Umeå University's logo

umu.sePublications
Change search
Refine search result
12 1 - 50 of 59
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Amhare, Abebe Feyissa
    et al.
    School of Public Health, Xi’an Jiaotong University, Health Science Center, Xi’an, Shaanxi, China.
    Jian, Lei
    School of Public Health, Xi’an Jiaotong University, Health Science Center, Xi’an, Shaanxi, China; Shenzhen Institute, Xi’an Jiaotong University, Shenzhen, Guangzhou, China.
    Wagaw, Lealem Minwuyelet
    Collage of Health Science, Salale University, Fitche, Ethiopia.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Han, Jing
    School of Public Health, Xi’an Jiaotong University, Health Science Center, Xi’an, Shaanxi, China; Shenzhen Institute, Xi’an Jiaotong University, Shenzhen, Guangzhou, China.
    Magnitude and associated factors of perceived stress and its consequence among undergraduate students of Salale University, Ethiopia: cross-sectional study2021In: Psychology, Health & Medicine, ISSN 1354-8506, E-ISSN 1465-3966, Vol. 26, no 10, p. 1230-1240Article in journal (Refereed)
    Abstract [en]

    Excessive stress may have a negative impact on students' performance and learning ability. The aim of this study is to assess the magnitude and associated factors of perceived stress and its consequences among undergraduate students at Salale University, Ethiopia. A self-administered cross-sectional study has been conducted among 421 students of Salale University from April 1(st) to May 30(th), 2018. Multiple linear regressions and Spearman's rank correlation were applied. The overall response rate is 95.49 %. The mean perceived stress score (PSS-14) was 29.97 (standard deviation =7.48). Spearman correlation test has shown that perceived stress is significantly but negatively correlated with grade point average [r(s) = -0.25 (-0.334 - -0.153)] and year of studies [r(s) = -0.13 (-0.232 - -0.032)]. Increased perceived stress indices are significantly associated with female gender (P < 0.001), grade point average (P < 0.01), academic stressors (P < 0.01), and psychosocial stressors (P < 0.01). Mean of PSS-14 was high among health science students (31.42 +/- 9.37) than agricultural (30.78 +/- 7.69) and business students (28.04 +/- 5.43), however, there were no statistically significant differences. These findings are sufficient to allow a large-scale study to further help better understanding the stress-vulnerability factors of undergraduate students.

  • 2.
    Arasu, Uma Thanigai
    et al.
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Kärnä, Riikka
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Härkönen, Kai
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Oikari, Sanna
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Koistinen, Arto
    SIB Labs, University of Eastern Finland, Kuopio, Finland.
    Kröger, Heikki
    Department of Orthopaedics and Traumatology, Kuopio University Hospital, Kuopio, Finland; Bone and Cartilage Research Unit, Surgery, Institute of Clinical Medicine, University of Eastern, Finland.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, PR China.
    Rilla, Kirsi
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Human mesenchymal stem cells secrete hyaluronan-coated extracellular vesicles2017In: Matrix Biology, ISSN 0945-053X, E-ISSN 1569-1802, Vol. 64, p. 54-68Article in journal (Refereed)
    Abstract [en]

    Extracellular vesicles (EVs) secreted by stem cells are potential factors mediating tissue regeneration. They travel from bone marrow stem cells into damaged tissues, suggesting that they can repair tissue injuries without directly replacing parenchymal cells. We have discovered that hyaluronan (HA) synthesis is associated with the shedding of HA-coated EVs. The aim of this study was to test whether bone marrow-derived hMSCs secrete HA-coated EVs. The EVs secreted by MSCs were isolated by differential centrifugation and characterized by nanoparticle tracking analysis. Their morphology and budding mechanisms were inspected by confocal microscopy and correlative light and electron microscopy. Hyaluronan synthesis of hMSCs was induced by lipopolysaccharide and inhibited by RNA interference and 4-methylumbelliferone. It was found that the MSCs have extremely long apical and lateral HA-coated filopodia, typical for cells with an active HA secretion. Additionally, they secreted HA-coated EVs carrying mRNAs for CD44 and all HAS isoforms. The results show that stem cells have a strong intrinsic potential for HA synthesis and EV secretion, and the amount of HA carried on EVs reflects the HA content of the original cells. These results show that the secretion of HA-coated EVs by hMSCs is a general process, that may contribute to many of the mechanisms of HA-mediated tissue regeneration. Additionally, an HA coat on EVs may regulate their interactions with target cells and participate in extracellular matrix remodeling.

  • 3.
    Deng, Huan
    et al.
    School of Public Health, Xi’an Jiaotong University Health Science Center, Shaanxi, Xi’an, China.
    Liu, Haobiao
    School of Public Health, Xi’an Jiaotong University Health Science Center, Shaanxi, Xi’an, China.
    Yang, Zhihao
    School of Public Health, Xi’an Jiaotong University Health Science Center, Shaanxi, Xi’an, China.
    Bao, Miaoye
    School of Public Health, Xi’an Jiaotong University Health Science Center, Shaanxi, Xi’an, China.
    Lin, Xue
    School of Public Health, Xi’an Jiaotong University Health Science Center, Shaanxi, Xi’an, China.
    Han, Jing
    School of Public Health, Xi’an Jiaotong University Health Science Center, Shaanxi, Xi’an, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Progress of selenium deficiency in the pathogenesis of arthropathies and selenium supplement for their treatment2022In: Biological Trace Element Research, ISSN 0163-4984, E-ISSN 1559-0720, Vol. 200, p. 4238-4249Article, review/survey (Refereed)
    Abstract [en]

    Selenium, an essential trace element for human health, exerts an indispensable effect in maintaining physiological homeostasis and functions in the body. Selenium deficiency is associated with arthropathies, such as Kashin-Beck disease, rheumatoid arthritis, osteoarthritis, and osteoporosis. Selenium deficiency mainly affects the normal physiological state of bone and cartilage through oxidative stress reaction and immune reaction. This review aims to explore the role of selenium deficiency and its mechanisms existed in the pathogenesis of arthropathies. Meanwhile, this review also summarized various experiments to highlight the crucial functions of selenium in maintaining the homeostasis of bone and cartilage.

  • 4.
    Deng, Huan
    et al.
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Xiao, Xiang
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Chilufya, Mumba Mulutula
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Qiao, Lichun
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Lv, Yizhen
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Guo, Ziwei
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Lei, Jian
    School of Public Health, Shanghai Medical College of Fudan University, Shanghai, China.
    Liu, Jiaxin
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Zhao, Yan
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Zhang, Jiaheng
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Wang, Wenyue
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Han, Jing
    School of Public Health, Xi'an Jiaotong University, Health Science Center, Xi'an, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Altered Expression of the Hedgehog Pathway Proteins BMP2, BMP4, SHH, and IHH Involved in Knee Cartilage Damage of Patients With Osteoarthritis and Kashin-Beck Disease2022In: Cartilage, ISSN 1947-6035, E-ISSN 1947-6043, Vol. 13, no 1, article id 19476035221087706Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the expression of Hedgehog (HH) signaling pathway proteins in knee articular cartilage from Kashin-Beck disease (KBD) and osteoarthritis (OA) patients.

    METHODS: Knee articular cartilage samples were collected from normal (N), OA, and KBD adults (aged 38-60 years) and divided into 3 groups with 6 subjects in each group. The localization of the HH pathway proteins bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 4 (BMP4), Sonic hedgehog (SHH), and Indian hedgehog (IHH) was observed with the microscope after immunohistochemical (IHC) staining. Positive staining cell rates of each proteins were compared.

    RESULTS: The strongest stainings of all proteins were observed in the middle zones of all 3 groups. The positive staining rates of BMP4 and IHH were significantly lower in the OA and KBD groups than those in the N group in all 3 zones. The positive staining rates of BMP2 and SHH tend to be lower in the OA and KBD groups than those in the N group in the deep zone, while higher in the OA and KBD groups than those in the N group in superficial and middle zones.

    CONCLUSIONS: Altered expression of the HH pathway proteins BMP2, BMP4, SHH, and IHH was found in OA and KBD articular cartilage. There seemed to be a compensatory effect between SHH and IHH in cartilage damage. Further studies on the pathogenesis of OA and KBD may be carried out from these aspects in the future.

    Download full text (pdf)
    fulltext
  • 5.
    Florea, Cristina
    et al.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Tanska, Petri
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Mononen, Mika
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center of Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Laasanen, Mikko
    School of Engineering and Technology, Savonia University of Applied Sciences, Kuopio, Finland.
    Korhonen, Rami
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland.
    A combined experimental atomic force microscopy-based nanoindentation and computational modeling approach to unravel the key contributors to the time-dependent mechanical behavior of single cells2017In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 16, no 1, p. 297-311, article id 27554263Article in journal (Refereed)
    Abstract [en]

    Cellular responses to mechanical stimuli are influenced by the mechanical properties of cells and the surrounding tissue matrix. Cells exhibit viscoelastic behavior in response to an applied stress. This has been attributed to fluid flow-dependent and flow-independent mechanisms. However, the particular mechanism that controls the local time-dependent behavior of cells is unknown. Here, a combined approach of experimental AFM nanoindentation with computational modeling is proposed, taking into account complex material behavior. Three constitutive models (porohyperelastic, viscohyperelastic, poroviscohyperelastic) in tandem with optimization algorithms were employed to capture the experimental stress relaxation data of chondrocytes at 5 % strain. The poroviscohyperelastic models with and without fluid flow allowed through the cell membrane provided excellent description of the experimental time-dependent cell responses (normalized mean squared error (NMSE) of 0.003 between the model and experiments). The viscohyperelastic model without fluid could not follow the entire experimental data that well (NMSE = 0.005), while the porohyperelastic model could not capture it at all (NMSE = 0.383). We also show by parametric analysis that the fluid flow has a small, but essential effect on the loading phase and short-term cell relaxation response, while the solid viscoelasticity controls the longer-term responses. We suggest that the local time-dependent cell mechanical response is determined by the combined effects of intrinsic viscoelasticity of the cytoskeleton and fluid flow redistribution in the cells, although the contribution of fluid flow is smaller when using a nanosized probe and moderate indentation rate. The present approach provides new insights into viscoelastic responses of chondrocytes, important for further understanding cell mechanobiological mechanisms in health and disease.

  • 6.
    Guo, Xiong
    et al.
    Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University, Xi'an, China.
    Ma, Wei-Juan
    Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University, Xi'an, China.
    Zhang, Feng
    Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University, Xi'an, China.
    Ren, Feng-Lin
    Institute of Endemic Diseases, School of Public Health, Xi'an Jiaotong University, Xi'an, China.
    Qu, Cheng-Juan
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Recent advances in the research of an endemic osteochondropathy in China: Kashin-Beck disease2014In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 22, no 11, p. 1774-1783, article id 25106677Article, review/survey (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD) is an endemic chronic osteochondral disease, which has a high prevalence and morbidity in the Eastern Siberia of Russia, and in the broad diagonal, northern-east to southern-west belt in China and North Korea. In 1990's, it was estimated that in China 1–3 million people had some degree of symptoms of the disease, although even higher estimates have been presented. In China, the extensive prevalence peaked in the late 1950's, but since then, in contrast to the global trend of the osteoarthritis (OA), the number of cases has been dramatically falling. Up to 2013, there are 0.64 millions patients with the KBD and 1.16 millions at risk in 377 counties of 13 provinces or autonomous regions. This is obviously thanks to the preventive efforts carried out, which include providing millions of people with dietary supplements and clean water, as well as relocation of whole villages in China. However, relatively little is known about the molecular mechanisms behind the cartilage damage, the genetic and the environmental risk factors, and the rationale of the preventive effects. During the last decade, new data on a cellular and molecular level has begun to accumulate, which hopefully will uncover the grounds of the disease.

  • 7. Guo, Yijie
    et al.
    Zhou, Yuan
    Yan, Siqi
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Wang, Liyun
    Guo, Xiong
    Han, Jing
    Decreased expression of CHST-12, CHST-13, and UST in the proximal interphalangeal joint cartilage of school-age children with Kashin-Beck disease: an endemic osteoarthritis in China caused by selenium deficiency2019In: Biological Trace Element Research, ISSN 0163-4984, E-ISSN 1559-0720, Vol. 191, no 2, p. 276-285Article in journal (Refereed)
    Abstract [en]

    The objective of this study is to investigate changes in the expression of enzymes involved in chondroitin sulfate (CS) sulfation in distal articular surface of proximal interphalangeal joint isolated from school-age children patients with Kashin-Beck disease (KBD), using normal children as controls. Articular cartilage samples were collected from four normal and four KBD children (7-12 years old), and these children were assigned to control and KBD groups. Hematoxylin and eosin (H&E), toluidine blue (TB), and immunohistochemical (IHC) stainings were utilized to evaluate changes in joint pathology and expression of enzymes involved in CS sulfation, including carbohydrate sulfotransferase 12 (CHST-12), carbohydrate sulfotransferase 13 (CHST-13), and uronyl 2-O-sulfotransferase (UST). The correspondence results were examined by semi-quantitative analysis. Compared with the control group, the KBD group showed the following: a significant decrease of total chondrocytes in superficial, middle, and deep layers and deposition of sulfated glycosaminoglycans in extracellular matrix of KBD cartilage were observed; positive staining chondrocytes of CHST-12, CHST-13, and UST were significantly less in superficial zone of KBD cartilage; and CHST-13 positive staining chondrocytes was reduced in deep zone of KBD cartilage. In contrast, the positive staining rates of CHST-12, CHST-13, and UST in KBD were significantly higher than those in the control group. The decreased expression of these enzymes and the physiologic compensatory reaction may be the signs of early-stage KBD. The alterations of CS structure modifying sulfotransferases in finger articular cartilage might play an important role in the onset and pathogenesis of school-age KBD children.

  • 8.
    Han, Jing
    et al.
    Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, China; Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
    Deng, Huan
    Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China; Global Health Institute, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
    Li, Yang
    CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, China.
    Qiao, Lichun
    Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
    Jia, Hongrui
    Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education and International Center for Dielectric Research, School of Electronic Science and Engineering, Xi'an Jiaotong University, Xi'an, China.
    Zhang, Lan
    State-key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, China.
    Wang, Linghang
    Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education and International Center for Dielectric Research, School of Electronic Science and Engineering, Xi'an Jiaotong University, Xi'an, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nano-elemental selenium particle developed via supramolecularself-assembly of chondroitin sulfate A and Na2SeO3 to repaircartilage lesions2023In: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 316, article id 121047Article in journal (Refereed)
    Abstract [en]

    Cartilage repair is a significant clinical issue due to its restricted ability to regenerate and self-heal after cartilage lesions or degenerative disease. Herein, a nano-elemental selenium particle (chondroitin sulfate A‑selenium nanoparticle, CSA-SeNP) is developed by the supramolecular self-assembly of Na2SeO3 and negatively charged chondroitin sulfate A (CSA) via electrostatic interactions or hydrogen bonds followed by in-situ reducing of l-ascorbic acid for cartilage lesions repair. The constructed micelle exhibits a hydrodynamic particle size of 171.50 ± 2.40 nm and an exceptionally high selenium loading capacity (9.05 ± 0.03 %) and can promote chondrocyte proliferation, increase cartilage thickness, and improve the ultrastructure of chondrocytes and organelles. It mainly enhances the sulfation modification of chondroitin sulfate by up-regulating the expression of chondroitin sulfate 4-O sulfotransferase-1, −2, −3, which in turn promotes the expression of aggrecan to repair articular and epiphyseal-plate cartilage lesions. The micelles combine the bio-activity of CSA with selenium nanoparticles (SeNPs), which are less toxic than Na2SeO3, and low doses of CSA-SeNP are even superior to inorganic selenium in repairing cartilage lesions in rats. Thus, the developed CSA-SeNP is anticipated to be a promising selenium supplementation preparation in clinical application to address the difficulty of healing cartilage lesions with outstanding repair effects.

  • 9.
    Han, Jing
    et al.
    School of public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
    Guo, Xiong
    School of public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
    Wang, Liyun
    School of public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
    Chilufya, Mumba Mulutula
    School of public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
    Lim, Poon Nian
    Department of Mechanical Enginnering, National University of Singapore, Singapore, Singapore.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Selenium deficiency and selenium supplements: biological effects on fibrosisin chronic diseases, from animal to human studies2019In: Handbook of famine, starvation, and nutrient deprivation: from biology to policy / [ed] Victor R. Preedy; Vinood B. Patel, Springer, 2019, p. 1911-1930Chapter in book (Refereed)
    Abstract [en]

    Selenium is a trace element, which is required for normal growth and development of animals and humans. It works by incorporating into proteins to make selenoproteins. These selenoproteins help to prevent free radicals from causing cellular damage, which may in turn lead to the development of various chronic diseases. Selenium deficiency, although is rare, can happen when the body does not have enough selenium. This chapter will review systematically the effects of selenium deficiency on fibrosis in various chronic diseases, such as cardiac fibrosis, liver fibrosis, kidney fibrosis, cystic fibrosis, thyroid fibrosis, oral submucous fibrosis, and pancreatic fibrosis in both animal and human studies. Moreover, their prevention and treatment with selenium supplement will be evaluated as well.

  • 10.
    Han, Jing
    et al.
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR China; Biomat lab, Department of Mechanical Engineering, National University of Singapore, Singapore.
    Li, Danyang
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Wang, Dong
    Biomat lab, Department of Mechanical Engineering, National University of Singapore, 117576, Singapore; Department of Orthopedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
    Wang, Liyun
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR Chin.
    Guo, Xiong
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR Chin.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.
    Altered expression of chondroitin sulfate structure modifying sulfotransferases in the articular cartilage from adult osteoarthritis and Kashin-Beck disease2017In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 25, no 8, p. 1372-1375, article id 28274888Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the expression of enzymes involved in chondroitin sulfate (CS) sulfation in the articular cartilage isolated from adult patients with osteoarthritis (OA) and Kashin-Beck disease (KBD), using normal adults as controls.

    METHODS: Articular cartilage samples were collected from normal, OA and KBD adults aged 38-60 years old, and divided into three groups with six individual subjects in each group. The morphology and pathology grading of knee joint cartilage was examined by Safranin O staining. The localization and expression of enzymes involved in CS sulfation (CHST-3, CHST-11, CHST-12, CHST-13, CHST-15, and UST) were examined by immunohistochemical staining and semi-quantitative analysis.

    RESULTS: Positive staining rates for anabolic enzymes CHST-3, CHST-12, CHST-15, and UST were lower in the KBD and OA groups than those in the control group. Meanwhile, reduced levels of CHST-11, and CHST-13 in KBD group were observed, in contrast to those in OA and control groups. The expressions of all six CS sulfation enzymes were less detected in the superficial and deep zones of KBD cartilage compared with control and OA cartilage.

    CONCLUSION: The reduced expression of the CS structure modifying sulfotransferases in the chondrocytes of both KBD and OA adult patients may provide explanations for their cartilage damages, and therapeutic targets for their treatment.

  • 11.
    Han, Jing
    et al.
    School of Public Health, Health Science Center, Xi’an Jiaotong University, No.76 Yanta West Road, Xi’an 710061, Shaanxi, People’s Republic of China.
    Wang, Weizhuo
    Department of Orthopedics, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, People’s Republic of China.
    Qu, Chengjuan
    Department of Applied Physics, University of Eastern Finland, 70211 Kuopio, Finland.
    Liu, Ruiyu
    Department of Orthopedics, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, People’s Republic of China.
    Li, Wenrong
    Department of Medical Imaging, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, People’s Republic of China.
    Gao, Zongqiang
    Department of Orthopedics, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, People’s Republic of China.
    Guo, Xiong
    School of Public Health, Health Science Center, Xi’an Jiaotong University, No.76 Yanta West Road, Xi’an 710061, Shaanxi, People’s Republic of China.
    Role of inflammation in the process of clinical Kashin-Beck disease: latest findings and interpretations2015In: Inflammation Research, ISSN 1023-3830, E-ISSN 1420-908X, Vol. 64, no 11, p. 853-860Article in journal (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD), a particular type of osteoarthritis (OA), and an endemic disease with articular cartilage damage and chondrocytes apoptosis, can affect many joints, and the most commonly affected joints are the knee, ankle, and hand. KBD has traditionally been classified as a non-inflammatory OA. However, recent studies have shown that inflammation has played an important role in the development of KBD. Nowadays, clinical KBD is not only an endemic disease, but also a combined result of many other non-endemic factors, which contains age, altered biomechanics, joint trauma and secondary OA. The characteristics of the developmental joint failure of advanced KBD, because of the biochemical and mechanical processes, are tightly linked with the interaction of joint damage and its immune response, as well as the subsequent state of chronic inflammation leading to KBD progression. In this review, we focus on the epidemiology, pathology, imaging, cytokines and transduction pathways investigating the association of inflammation with KBD; meanwhile, a wide range of data will be discussed to elicit our current hypotheses considering the role of inflammation and immune activation in KBD development.

  • 12.
    Han, Jing
    et al.
    College of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
    Yu, Fang Fang
    College of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
    Chang, Zai Ping
    Department of Surgery, The Second Hospital of Weinan City, Weinan, China.
    Yang, Bo
    Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
    Qu, Cheng Juan
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Zhou, Tian Tian
    College of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
    Liu, Rui Yu
    Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
    Guo, Xiong
    College of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
    Changing grains for the prevention and treatment of Kashin-Beck disease in children: a Meta-analysis2015In: Biomedical and environmental sciences, ISSN 0895-3988, E-ISSN 2214-0190, Vol. 28, no 4, p. 308-311Article in journal (Refereed)
    Abstract [en]

    To evaluate the efficacy of changing grains on the prevention and treatment of Kashin-Beck Disease (KBD) in children, community-based trials were acquired from seven electronic databases (up to July 2014). As a result, the methodological quality of the six trials that have been included into our analysis was low. The pooled ORs favoring the prevention and treatment effects of changing grains were 0.15 (95% CI: 0.03-0.70) and 2.13 (95% CI: 1.44-3.16) respectively by meta-analysis. Subgroup analysis demonstrated the pooled OR favoring treatment effect of exchanging grains rather than drying grains both compared with endemic grains. The results showed that changing grains had obvious effects on the prevention and treatment of KBD in children. However, the evidences were limited by the potential biases and confounders. Large and well-designed trials are still needed.

  • 13.
    He, Shu-Lan
    et al.
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Tan, Wu-Hong
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Zhang, Zeng-Tie
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Zhang, Feng
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Qu, Cheng-Juan
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Lei, Yan-Xia
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Zhu, Yan-He
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Yu, Han-Jie
    Department of Biotechnology, Northwest University, Xi'an, China.
    Xiang, You-Zhang
    Shandong Institute for prevention & Treatment of Endemic Disease, Jinan, China.
    Guo, Xiong
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy.2013In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 319, no 17, p. 2604-2616, article id 23954821Article in journal (Refereed)
    Abstract [en]

    Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4 × 44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios ≥ 2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD.

  • 14.
    Julkunen, Petro
    et al.
    Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland; Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland.
    Wilson, Wouter
    Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
    Jurvelin, Jukka
    Department of Physics, University of Kuopio, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
    Rieppo, Jarno
    Department of Biomedicine, Anatomy, University of Kuopio, Kuopio, FinlandDepartment of Biomedicine, Anatomy, University of Kuopio, Kuopio, Finland.
    Qu, Cheng-Juan
    Department of Biomedicine, Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Korhonen, Rami
    Department of Physics, University of Kuopio, Kuopio, Finland; Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.
    Stress-relaxation of human patellar articular cartilage in unconfined compression: prediction of mechanical response by tissue composition and structure.2008In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 41, no 9, p. 1978-86, article id 18490021Article in journal (Refereed)
    Abstract [en]

    Mechanical properties of articular cartilage are controlled by tissue composition and structure. Cartilage function is sensitively altered during tissue degeneration, in osteoarthritis (OA). However, mechanical properties of the tissue cannot be determined non-invasively. In the present study, we evaluate the feasibility to predict, without mechanical testing, the stress-relaxation response of human articular cartilage under unconfined compression. This is carried out by combining microscopic and biochemical analyses with composition-based mathematical modeling. Cartilage samples from five cadaver patellae were mechanically tested under unconfined compression. Depth-dependent collagen content and fibril orientation, as well as proteoglycan and water content were derived by combining Fourier transform infrared imaging, biochemical analyses and polarized light microscopy. Finite element models were constructed for each sample in unconfined compression geometry. First, composition-based fibril-reinforced poroviscoelastic swelling models, including composition and structure obtained from microscopical and biochemical analyses were fitted to experimental stress-relaxation responses of three samples. Subsequently, optimized values of model constants, as well as compositional and structural parameters were implemented in the models of two additional samples to validate the optimization. Theoretical stress-relaxation curves agreed with the experimental tests (R=0.95-0.99). Using the optimized values of mechanical parameters, as well as composition and structure of additional samples, we were able to predict their mechanical behavior in unconfined compression, without mechanical testing (R=0.98). Our results suggest that specific information on tissue composition and structure might enable assessment of cartilage mechanics without mechanical testing.

  • 15.
    Kaitainen, Salla
    et al.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Mähönen, Anssi
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Lappalainen, Reijo
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Kröger, Heikki
    Department of Orthopaedics and Traumatology, Kuopio University Hospital, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Qu, Chengjuan
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    TiO2 coating promotes human mesenchymal stem cell proliferation without the loss of their capacity for chondrogenic differentiation2013In: Biofabrication, ISSN 1758-5090, Vol. 5, no 2, p. 025009-, article id 23592549Article in journal (Refereed)
    Abstract [en]

    Human mesenchymal stem cells (hMSCs) are used in applications, which may require a large amount of cells; therefore, efficient expansion of the cells is desired. We studied whether TiO2 coating on plastic cell culture dishes could promote proliferation of hMSCs without adverse effects in chondrogenic differentiation. TiO2-films were deposited on polystyrene dishes and glass coverslips using an ultrashort pulsed laser deposition technique. Human MSCs from three donors were expanded on them until 95% confluence, and the cells were evaluated by morphology, immunocytochemistry and quantitative RT-PCR (qRT-PCR). The chondrogenic differentiation in pellets was performed after cultivation on TiO2-coated dishes. Chondrogenesis was evaluated by histological staining of proteoglycans and type II collagen, and qRT-PCR. Human MSC-associated markers STRO-1, CD44, CD90 and CD146 did not change after expansion on TiO2-coated coverslips. However, the cell number after a 48h-culture period was significantly higher on TiO2-coated culture dishes. Importantly, TiO2 coating caused no significant differences in the proteoglycan and type II collagen staining of the pellets, or the expression of chondrocyte-specific genes in the chondrogenesis assay. Thus, the proliferation of hMSCs could be significantly increased when cultured on TiO2-coated dishes without weakening their chondrogenic differentiation capacity. The transparency of TiO2-films allows easy monitoring of the cell growth and morphology under a phase-contrast microscope.

  • 16.
    Karjalainen, Hannu
    et al.
    School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Qu, Chengjuan
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Leskelä, Stina
    School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Rilla, Kirsi
    School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Chondrocytic cells express the taurine transporter on their plasma membrane and regulate its expression under anisotonic conditions2015In: Amino Acids, ISSN 0939-4451, E-ISSN 1438-2199, Vol. 47, no 3, p. 561-570Article in journal (Refereed)
    Abstract [en]

    Taurine is a small organic osmolyte which participates in cell volume regulation. Chondrocytes have been shown to accumulate and release taurine; in bone, taurine participates in bone metabolism. However, its role in skeletal cells is poorly understood, especially in chondrocytes. This study investigated the regulation of taurine transporter in chondrocytic cells. We examined the transcriptional regulation of the taurine transporter under anisotonia by reporter gene and real-time RT-PCR assays. The effect of providing supplementary taurine on cell viability was evaluated with the lactate dehydrogenase release assay. The localization of the taurine transporter in human chondrosarcoma cells was studied by overexpressing a taurine transporter-enhanced green fluorescent protein. We observed that the transcription of the taurine transporter gene was up-regulated in hypertonic conditions. Hyperosmolarity-related cell death could be partly abolished by taurine supplementation in the medium. As expected, the fluorescently labeled taurine transporter localized at the plasma membrane. In polarized epithelial MDCK cells, the strongest fluorescence signal was located in the lateral cell membrane area. We also observed that the taurine transporter gene was expressed in several human tissues and malignant cell lines. This is the first study to present information on the transcriptional regulation of taurine transporter gene and the localization of the taurine transporter protein in chondrocytic cells.

  • 17.
    Koskinen Holm, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Engineering a 3D In Vitro Model of Human Gingival Tissue Equivalent with Genipin/Cytochalasin D2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 13, article id 7401Article in journal (Refereed)
    Abstract [en]

    Although three-dimensional (3D) co-culture of gingival keratinocytes and fibroblasts-populated collagen gel can mimic 3D structure of in vivo tissue, the uncontrolled contraction of collagen gel restricts its application in clinical and experimental practices. We here established a stable 3D gingival tissue equivalent (GTE) using hTERT-immortalized gingival fibroblasts (hGFBs)-populated collagen gel directly crosslinked with genipin/cytochalasin D and seeding hTERT-immortalized gingival keratinocytes (TIGKs) on the upper surface for a 2-week air–liquid interface co-culture. MTT assay was used to measure the cell viability of GTEs. GTE size was monitored following culture period, and the contraction was analyzed. Immunohistochemical assay was used to analyze GTE structure. qRT-PCR was conducted to examine the mRNA expression of keratinocyte-specific genes. Fifty µM genipin (G50) or combination (G + C) of G50 and 100 nM cytochalasin D significantly inhibited GTE contraction. Additionally, a higher cell viability appeared in GTEs crosslinked with G50 or G + C. GTEs crosslinked with genipin/cytochalasin D showed a distinct multilayered stratified epithelium that expressed keratinocyte-specific genes similar to native gingiva. Collagen directly crosslinked with G50 or G + C significantly reduced GTE contraction without damaging the epithelium. In summary, the TIGKs and hGFBs can successfully form organotypic multilayered cultures, which can be a valuable tool in the research regarding periodontal disease as well as oral mucosa disease. We conclude that genipin is a promising crosslinker with the ability to reduce collagen contraction while maintaining normal cell function in collagen-based oral tissue engineering.

    Download full text (pdf)
    fulltext
  • 18.
    Lammi, Mikko
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning, Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi'an Jiaotong University, Xi'an, China.
    Piltti, Juha
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Nordlab Kokkola, Keski-Pohjanmaa Central Hospital Soite, Kokkola, Finland.
    Prittinen, Juha
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Challenges in fabrication of tissue-engineered cartilage with correct cellular colonization and extracellular matrix assembly2018In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 19, no 9, article id 2700Article, review/survey (Refereed)
    Abstract [en]

    A correct articular cartilage ultrastructure regarding its structural components and cellularity is important for appropriate performance of tissue-engineered articular cartilage. Various scaffold-based, as well as scaffold-free, culture models have been under development to manufacture functional cartilage tissue. Even decellularized tissues have been considered as a potential choice for cellular seeding and tissue fabrication. Pore size, interconnectivity, and functionalization of the scaffold architecture can be varied. Increased mechanical function requires a dense scaffold, which also easily restricts cellular access within the scaffold at seeding. High pore size enhances nutrient transport, while small pore size improves cellular interactions and scaffold resorption. In scaffold-free cultures, the cells assemble the tissue completely by themselves; in optimized cultures, they should be able to fabricate native-like tissue. Decellularized cartilage has a native ultrastructure, although it is a challenge to obtain proper cellular colonization during cell seeding. Bioprinting can, in principle, provide the tissue with correct cellularity and extracellular matrix content, although it is still an open question as to how the correct molecular interaction and structure of extracellular matrix could be achieved. These are challenges facing the ongoing efforts to manufacture optimal articular cartilage.

    Download full text (pdf)
    fulltext
  • 19.
    Lammi, Mikko
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning, Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Xi’an, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Selenium-related transcriptional regulation of gene expression2018In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 19, no 9, article id 2665Article, review/survey (Refereed)
    Abstract [en]

    The selenium content of the body is known to control the expression levels of numerous genes, both so-called selenoproteins and non-selenoproteins. Selenium is a trace element essential to human health, and its deficiency is related to, for instance, cardiovascular and myodegenerative diseases, infertility and osteochondropathy called Kashin⁻Beck disease. It is incorporated as selenocysteine to the selenoproteins, which protect against reactive oxygen and nitrogen species. They also participate in the activation of the thyroid hormone, and play a role in immune system functioning. The synthesis and incorporation of selenocysteine occurs via a special mechanism, which differs from the one used for standard amino acids. The codon for selenocysteine is a regular in-frame stop codon, which can be passed by a specific complex machinery participating in translation elongation and termination. This includes a presence of selenocysteine insertion sequence (SECIS) in the 3'-untranslated part of the selenoprotein mRNAs. Nonsense-mediated decay is involved in the regulation of the selenoprotein mRNA levels, but other mechanisms are also possible. Recent transcriptional analyses of messenger RNAs, microRNAs and long non-coding RNAs combined with proteomic data of samples from Keshan and Kashin⁻Beck disease patients have identified new possible cellular pathways related to transcriptional regulation by selenium.

    Download full text (pdf)
    fulltext
  • 20.
    Lammi, Mikko
    et al.
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Qu, Cheng-Juan
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Laasanen, Mikko
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Saarakkala, Simo
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Rieppo, Jarno
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Töyräs, Juha
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Undersulfated chondroitin sulfate does not increase in osteoarthritic cartilage.2004In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 31, no 12, p. 2449-2453, article id 15570650Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To test whether there is undersulfation of chondroitin sulfate in osteoarthritic bovine articular cartilage to support the hypothesis that sulfate deficiency is involved with the development of osteoarthritis.

    METHODS: Cartilage samples from bovine patellae (n = 32) were divided into 3 groups based on their osteoarthritic progression, as assessed by modified Mankin score. Uronic acid contents of the samples were determined. Fragmentation of the proteoglycans due to proteolytic processing was estimated with agarose gel electrophoresis. The molar ratios of chondroitin sulfate isoforms in the extracted proteoglycans were determined with fluorophore-assisted carbohydrate electrophoresis.

    RESULTS: Loss of proteoglycans and accumulation of tissue water was evident in groups II and III, and progressive OA increased heterogeneity of aggrecan population in groups II and III. Importantly, the molar ratio of nonsulfated disaccharide was decreased in the osteoarthritic articular cartilage.

    CONCLUSION: The structure of chondroitin sulfate in degenerated bovine cartilage did not support the hypothesis that sulfate depletion is present in osteoarthritic joint.

  • 21.
    Lammi, Mikko
    et al.
    Institute of Biomedicine, University of Eastern Finland.
    Qu, Chengjuan
    Institute of Biomedicine, University of Eastern Finland.
    Prittinen, Juha
    Institute of Biomedicine, University of Eastern Finland.
    Kröger, Heikki
    Department of Orthopaedics and Traumatology, Kuopio University Hospital, Kuopio, Finland.
    Koistinen, Arto
    SIB-Labs, University of Eastern Finland, Kuopio, Finland.
    Myllymaa, Sami
    SIB-Labs, University of Eastern Finland, Kuopio, Finland.
    Lappalainen, Reijo
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Adhesion and spreading of different skeletal celltypes on variable surface coatings2012In: 2012 5th International Conference on BioMedical Engineering and Informatics (BMEI 2012), IEEE, 2012, p. 582-587Conference paper (Refereed)
    Abstract [en]

    The adhesion and spreading of human bone marrow-derived mesenchymal stem cells (hMSCs), bovine primary chondrocytes and human osteoblastic osteosarcoma cell line (Saos-2) cultured on various coated surfaces were examined to determine whether different materials coated on the silicon wafer could affect the growth of the different cell types. The amorphous diamond (AD), titania (TiO2), alumina (Al2O3) or carbon nitride (C3N4) coating on the silicon wafer was obtained by using ultra short pulsed laser deposition. The differences in surface characteristics were characterized with atomic force microscope and contact angles and zeta potential measurements. Human MSCs, bovine primary chondrocytes and Saos-2 osteoblasts were cultured for 48 h in direct contact with AD-, TiO2-, Al2O3- and C3N4-coated surfaces. Cell proliferation was assayed with MTT assay. The morphology, adhesion and spreading of the cultured cells were examined with scanning electron microscope. Human MSCs had the highest cell number after 48-h-culture on all of the different coated surfaces, followed by Saos-2 osteoblasts, and then bovine primary chondrocytes. The morphological appearance of MSCs, chondrocytes and Saos-2 osteoblasts remained as original. No statistically significant differences on cell proliferation were found among the different coated surfaces. Ultra short pulsed laser deposited high quality AD-, TiO2-, Al2O3- and C3N4-coated surfaces, and provided a good environment for the adhesion and spreading of the hMSCs, primary chondrocytes and Saos-2 osteoblasts

  • 22.
    Lappalainen, Reijo
    et al.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Korhonen, Hannu
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Kaitainen, Salla
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Myllymaa, Sami
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Qu, Chengjuan
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nanostructured coatings for biomedical applications by ultra short pulsed laser deposition2015In: Comprehensive guide for nanocoatings technology: Volume 3, Properties and development / [ed] Mahmoud Aliofkhadzraei, Nova Science Publishers, Inc., 2015, 3, p. 309-323Chapter in book (Refereed)
    Abstract [en]

    Ultra short pulsed laser deposition (USPLD) technique is a novel, well-controlled physical vapour deposition method to deposit a wide variety of nanocoatings on solid substrate materials with good adhesion and various surface nanotopographies. Coating materials include ceramics, like Al2O3, TiO2, carbon nitride and amorphous diamond, metals, such as platinum, titanium and Ti6Al4V, as well as polymers, composite materials and so on. In this chapter, we demonstrate and review the possibilities of USPLD for modified biomaterial surfaces in medical applications, such as cell culture plates, electrodes or implants used in orthopaedics and dentistry. The coatings are used to control, e.g., cell growth and proliferation, bacterial adhesion, bioelectrical properties, corrosion, friction and wear.

  • 23.
    Lei, Jian
    et al.
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
    Yan, Siqi
    Shenzhen Institute, Xi'an Jiaotong University, China; Department of Ophthalmology, The First Affiliated Hospital, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
    Zhou, Yuan
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
    Wang, Liyun
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China; Shenzhen Institute, Xi'an Jiaotong University, Shenzhen, China.
    Zhang, Jinghua
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
    Guo, Xiong
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, P. R. China.
    Han, Jing
    Shenzhen Institute, Xi'an Jiaotong University, Shenzhen, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Abnormal expression of chondroitin sulfate sulfotransferases in the articular cartilage of pediatric patients with Kashin-Beck disease2020In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 153, no 3, p. 153-164Article in journal (Refereed)
    Abstract [en]

    The objective of this study is to investigate the expression of enzymes involved in the sulfation of articular cartilage from proximal metacarpophalangeal (PMC) joint cartilage and distal metacarpophalangeal (DMC) joint cartilage in children with Kashin-Beck disease (KBD). The finger cartilage samples of PMC and DMC were collected from KBD and normal children aged 5-14 years old. Hematoxylin and eosin staining as well as immunohistochemical staining were used to observe the morphology and quantitate the expression of carbohydrate sulfotransferase 3 (CHST-3), carbohydrate sulfotransferase 12 (CHST-12), carbohydrate sulfotransferase 13 (CHST-13), uronyl 2-O-sulfotransferase (UST), and aggrecan. In the results, the numbers of chondrocyte decreased in all three zones of PMC and DMC in the KBD group. Less positive staining cells for CHST-3, CHST-12, CHST-13, UST, and aggrecan were observed in almost all three zones of PMC and DMC in KBD. The positive staining cell rates of CHST-12 were higher in superficial and middle zones of PMC and DMC in KBD, and a significantly higher rate of CHST-13 was observed only in superficial zone of PMC in KBD. In conclusion, the abnormal expression of chondroitin sulfate sulfotransferases in chondrocytes of KBD children may provide an explanation for the cartilage damage, and provide therapeutic targets for the treatment.

  • 24.
    Li, Danyang
    et al.
    College of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.
    Han, Jing
    College of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.
    Guo, Xiong
    College of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Yu, Fangfang
    College of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.
    Wu, Xiaofang
    College of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.
    The effects of T-2 toxin on the prevalence and development of Kashin–Beck disease in China: a meta-analysis and systematic review2016In: Toxicology Research, ISSN 2045-4538, Vol. 5, no 3, p. 731-751Article, review/survey (Refereed)
    Abstract [en]

    To reveal the influence of T-2 toxin detection rate and detection amount in food samples on Kashin–Beck disease (KBD), and define a linking mechanism between T-2 toxin induced chondrocytes or cartilage damage and KBD pathological changes, seven electronic databases were searched to obtain epidemiological and experimental studies. For epidemiological studies, subgroup analyses of the positive detection rate (PDR) of the T-2 toxin and PDR of the T-2 toxin with concentrations (PDRC of T-2) >100 ng g−1 were carried out, together with a histogram of the T-2 toxin concentrations in different food types in KBD and non-KBD areas. For experimental studies, a systematic review of a variety of chondrocyte and cartilage changes and damage induced by the T-2 toxin was performed. As a result, in epidemiological studies, meta-analysis demonstrated that the T-2 toxin PDR and the overall PDRC of T-2 toxin >100 ng g−1 showed a slightly significant increase in KBD areas than that in non-KBD areas separately. From the histogram, T-2 toxin accumulation was more serious in endemic areas, especially in wheat flour samples. In experimental studies, the T-2 toxin could induce damage of chondrocytes and cartilage, and inhibit cell proliferation by promoting apoptosis and catabolism as well as intracellular injuries, which is similar to the characteristics of KBD. In conclusion, the amount of T-2 toxin detected has a more significant influence on KBD prevalence and development as compared to the T-2 toxin detection rate. Besides, the T-2 toxin induces chondrocyte and cartilage damage through apoptosis, catabolism promotion and intracellular impairment, which is similar to the KBD change.

  • 25.
    Li, Wenrong
    et al.
    Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China;School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
    Hirvasniemi, Jukka
    Center for Machine Vision and Signal Analysis, Faculty of Information Technology and Electrical Engineering, University of Oulu, Oulu, Finland.
    Guo, Xiong
    School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
    Saarakkala, Simo
    Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, P. R. China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Comparison of bone texture between normal individuals and patients with Kashin-Beck disease from plain radiographs in knee2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 17510Article in journal (Refereed)
    Abstract [en]

    To compare tibial bone texture between Kashin-Beck disease (KBD) patients and normal individuals from plain radiographs using an advanced image analysis. Plain knee radiographs were obtained from KBD patients (n = 49) and age-matched healthy controls (n = 98). KBD were graded with diagnostic criteria WS/T 207-2010. The textural values related to bone structure from medial and lateral tibial subchondral and trabecular bones were evaluated using entropy of Laplacian-based image (ELap), entropy of local binary patterns (ELBP), homogeneity indices (HI) of local angles (HIMean, HIPerp and HIParal), and fractal dimensions from horizontal (FDHor) and vertical (FDVer) structures. KBD patients were shorter in height and lighter in weight, and their tibial width was wider than controls. Anatomical angle of KBD patients showed more genu valgus. Total KBD patients and subgroups had higher ELap, HIMean, HIPerp and HIParal in detected tibial subchondral and trabecular bones than controls, except ELap in lateral subchondral bone. ELBP, FDHor and FDVer from the detected tibial bone in KBD patients and subgroups were lower than controls, except FDVer in lateral trabecular bone. Our results indicate that micro-scale in bone texture in KBD-affected knees can be quantitatively examined from plain radiographs using an advanced image analysis.

    Download full text (pdf)
    fulltext
  • 26.
    Liu, Huan
    et al.
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    Wu, Cuiyan
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    Zhao, Hongmou
    Department of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China.
    Zhang, Feng'e
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    Zhao, Guanghui
    Department of Joint Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China.
    Lin, Xialu
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    Wang, Sen
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    Wang, Xi
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    Yu, Fangfang
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    Ning, Yujie
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    Yang, Lei
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    Liu, Peilong
    Department of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China.
    Zhang, Feng
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    Xu, Peng
    Department of Foot and Ankle Surgery, Hong Hui Hospital of Xi'an Jiaotong University, Xi'an, P.R. China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center of Xi'an Jiaotong University, China.
    Guo, Xiong
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, P.R. China.
    The first human induced pluripotent stem cell line of Kashin–Beck disease reveals involvement of heparan sulfate proteoglycan biosynthesis and PPAR pathway2022In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 289, no 1, p. 279-293Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Kashin-Beck disease (KBD) is an endemic osteochondropathy. Due to a lack of suitable animal or cellular disease models, the research progress on KBD has been limited. Our goal was to establish the first disease-specific human induced pluripotent stem cells (hiPSCs) cellular disease model of KBD, and to explore its etiology and pathogenesis exploiting transcriptome sequencing.

    METHODS: HiPSCs were reprogrammed from dermal fibroblasts of two KBD and one healthy control donors via integration-free vectors. Subsequently, hiPSCs were differentiated into chondrocytes through three-week culture. Gene expression profiles in KBD, normal primary chondrocytes and hiPSC-derived chondrocytes were defined by RNA sequencing. A Venn diagram was constructed to show the number of shared differentially expressed genes (DEGs) between KBD and normal. Gene oncology and Kyoto Encyclopedia of Genes and Genomes annotations were performed, and six DEGs were further validated in other individuals by real-time quantitative reverse transcription PCR (RT-qPCR).

    RESULTS: KBD cellular disease models were successfully established by generation of hiPSC lines. Seventeen consistent and significant DEGs present in all compared groups (KBD and normal) were identified. RT-qPCR validation gave consistent results with the sequencing data. Glycosaminoglycan biosynthesis-heparan sulfate/heparin, PPAR signaling pathway and cell adhesion molecules (CAMs) pathways were identified to be significantly altered in KBD.

    CONCLUSION: Differentiated chondrocytes deriving from KBD-origin hiPSCs provide the first cellular disease model for etiological studies of KBD. This study also provides new sights into the pathogenesis and etiology of KBD and is likely to inform the development of targeted therapeutics for its treatment.

  • 27.
    Liu, Huan
    et al.
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Yang, Lei
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Yu, Fang Fang
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Wang, Sen
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Wu, Cuiyan
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Guo, Xiong
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    The potential of induced pluripotent stem cells as a tool to study skeletal dysplasias and cartilage-related pathologic conditions2017In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 25, no 5, p. 616-624, article id 27919783Article, review/survey (Refereed)
    Abstract [en]

    The development of induced pluripotent stem cells (iPSCs) technology has opened up new horizons for development of new research tools especially for skeletal dysplasias, which often lack human disease models. Regenerative medicine and tissue engineering could be the next areas to benefit from refinement of iPSC methods to repair focal cartilage defects, while applications for osteoarthritis (OA) and drug screening have evolved rather slowly. Although the advances in iPSC research of skeletal dysplasias and repair of focal cartilage lesions are not directly relevant to OA, they can be considered to pave the way to future prospects and solutions to OA research, too. The same problems which face the present cell-based treatments of cartilage injuries concern also the iPSC-based ones. However, established iPSC lines, which have no genomic aberrations and which efficiently differentiate into extracellular matrix secreting chondrocytes, could be an invaluable cell source for cell transplantations in the future. The safety issues concerning the recipient risks of teratoma formation and immune response still have to be solved before the potential use of iPSCs in cartilage repair of focal cartilage defects and OA.

  • 28. Lu, Xueliang
    et al.
    Wu, Junlong
    Qin, Yannan
    Liang, Jialin
    Qian, Hang
    Song, Jidong
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Liu, Ruiyu
    Identification of N-glycoproteins of hip cartilage in patients with osteonecrosis of femoral head using quantitative glycoproteomics2021In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 187, p. 892-902Article in journal (Refereed)
    Abstract [en]

    N-glycosylation is a major post-translational modification of proteins and involved in many diseases, however, the state and role of N-glycosylation in cartilage degeneration of osteonecrosis of femoral head (ONFH) remain unclear. The aim of this study is to identify the glycoproteins of ONFH hip cartilage. Cartilage tissues were collected from nine patients with ONFH and nine individuals with traumatic femoral neck fracture. Cartilage glycoproteins were identified by glycoproteomics based on LC-MS/MS. The differentially N-glycoproteins including glycosites were identified in ONFH and controls. A total of 408 N-glycoproteins with 444 N-glycosites were identified in ONFH and control cartilage. Among them, 104 N-glycoproteins with 130 N-glycosites were significantly differential in ONFH and control cartilage, which including matrix-remodeling-associated protein 5, prolow-density lipoprotein receptor-related protein 1, clusterin and lysosome-associated membrane glycoprotein 2. Gene Ontology analysis revealed the significantly differential glycoproteins mainly belonged to protein metabolic process, single-multicellular organism process, proteolysis, biological adhesion and cell adhesion. KEGG pathway and protein-protein interaction analysis suggested that the significantly differential glycoproteins were associated with PI3K-Akt signalling pathway, ECM-receptor interaction, protein processing in the endoplasmic reticulum and N-glycan biosynthesis. This information provides substantial insight into the role of protein glycosylation in the development of cartilage degeneration of ONFH patients.

  • 29.
    Lyu, Yizhen
    et al.
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Deng, Huan
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Qiao, Lichun
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Liu, Xuan
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Xiao, Xiang
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Liu, Jiaxin
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Guo, Ziwei
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Zhao, Yan
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Han, Jing
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
    Identification of proteins and N-glycosylation sites of knee cartilage in Kashin-Beck Disease compared with osteoarthritis2022In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 210, p. 128-138Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to identify crucial proteins and N-glycosylated sites in the pathological mechanism of Kashin-Beck Disease (KBD) compared with osteoarthritis (OA). Nine KBD knee subjects and nine OA knee subjects were selected for the study. Quantitative proteomics and N-glycoproteomics data of KBD and OA were obtained by protein and N-glycoprotein enrichment and LC-MS/MS analysis. Differentially expressed proteins or N-glycosylation sites were examined with a comparative analysis between KBD and OA. Total 2205 proteins were identified in proteomic analysis, of which 375 were significantly different. Among these, 121 proteins were up-regulated and 254 were down-regulated. In N-glycoproteomic analysis, 278 different N-glycosylated sites that were related to 187 N-glycoproteins were identified. Proteins and their N-glycosylated sites are associated with KBD pathological process including ITGB1, LRP1, ANO6, COL1A1, MXRA5, DPP4, and CSPG4. CRLF1 and GLG1 are proposed to associate with both KBD and OA pathological processes. Key pathways in KBD vs. OA proteomic and N-glycoproteomic analysis contained extracellular matrix receptor interaction, focal adhesion, phagosome, protein digestion, and absorption. N-glycosylation may influence the pathological process by affecting the integrity of chondrocytes or cartilage. It regulated the intercellular signal transduction pathway, which contributes to cartilage destruction in KBD.

  • 30.
    Piltti, Juha
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bygdell, Joakim
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Qu, Chenjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi’an, China.
    Effects of long-term hypoxia in human chondrosarcoma cells2018In: Journal of Cellular Biochemistry, ISSN 0730-2312, E-ISSN 1097-4644, Vol. 119, no 2, p. 2320-2332Article in journal (Refereed)
    Abstract [en]

    The cell-based therapies could be potential methods to treat damaged cartilage tissues. Instead of native hyaline cartilage, the current therapies generate mainly weaker fibrocartilage-type of repair tissue. A correct microenvironment influences the cellular phenotype, and together with external factors it can be used, e.g., to aid the differentiation of mesenchymal stem cells to defined types of differentiated adult cells. In this study, we investigated the effect of long-term exposure to 5% low oxygen atmosphere on human chondrosarcoma HCS-2/8 cells. This atmosphere is close to normal oxygen tension of cartilage tissue. The proteome was analyzed with label-free mass spectrometric method and further bioinformatic analysis. The qRT-PCR method was used to gene expression analysis, and ELISA and dimethylmethylene blue assays for type II collagen and sulfated glycosaminoglycan measurements. The hypoxic atmosphere did not influence cell proliferation, but enhanced slightly ACAN and COL2A1 gene expression. Proteomic screening revealed a number of hypoxia-induced protein level responses. Increased ones included NDUFA4L2, P4HA1, NDRG1, MIF, LDHA, PYGL, while TXNRD1, BAG2, TXN2, AQSTM1, TNFRSF1B and EPHX1 decreased during the long-term hypoxia. Also a number of proteins previously not related to hypoxia changed during the treatment. Of those S100P, RPSS26, NDUFB11, CDV3 and TUBB8 had elevated levels, while ALCAM, HLA-B, EIF1, and ACOT9 were lower in the hypoxia samples. In conclusion, low oxygen condition causes changes in the cellular amounts of several proteins.

  • 31.
    Piltti, Juha
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Varjosalo, Markku
    Institute of Biotechnology, University of Helsinki, Helsinki.
    Qu, Chengjuan
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Häyrinen, Jukka
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Rho-kinase inhibitor Y-27632 increases cellular proliferation and migration in human foreskin fibroblast cells2015In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 15, no 17, p. 2953-2965Article in journal (Refereed)
    Abstract [en]

    The idea of direct differentiation of somatic cells into other differentiated cell types has attracted a great interest recently. Rho-kinase inhibitor Y-27632 (ROCKi) is a potential drug molecule, which has been reported to support the gene expressions typical for the chondrocytes, thus restricting their phenotypic conversion to fibroblastic cells upon the cellular expansion. In this study, we have investigated the short-term biological responses of ROCKi to human primary foreskin fibroblasts. The fibroblast cells were exposed to 1 and 10 μM ROCKi treatments. A proteomics analysis revealed expression changes of 56 proteins, and a further protein pathway analysis suggested their association with the cell morphology, the organization, and the increased cellular movement and the proliferation. These functional responses were confirmed by a Cell-IQ time-lapse imaging analysis. Rho-kinase inhibitor treatment increased the cellular proliferation up to twofold during the first 12 h, and a wound model based migration assay showed 50% faster filling of the mechanically generated wound area. Additionally, significantly less vinculin-associated focal adhesions were present in the ROCKi-treated cells. Despite the marked changes in the cell behavior, ROCKi was not able to induce the expression of the chondrocyte-specific genes, such as procollagen α1 (II) and aggrecan.

  • 32.
    Prittinen, Juha
    et al.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Jiang, Yu
    Department of Chemistry, University of Eastern Finland, Joensuu, Finland.
    Ylärinne, Janne
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Pakkanen, Tapani
    Department of Chemistry, University of Eastern Finland, Joensuu, Finland.
    Lammi, Mikko
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Qu, Chengjuan
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Chondrocyte behavior on nanostructured micropillar polypropylene and polystyrene surfaces2014In: Materials Science and Engineering. C, Materials for Biological Applications, ISSN 0928-4931, Vol. 43, p. 424-431Article in journal (Refereed)
    Abstract [en]

    This study was aimed to investigate whether patterned polypropylene (PP) or polystyrene (PS) could enhance the chondrocytes' extracellular matrix (ECM) production and phenotype maintenance. Bovine primary chondrocytes were cultured on smooth PP and PS, as well as on nanostructured micropillar PP (patterned PP) and PS (patterned PS) for 2 weeks. Subsequently, the samples were collected for fluorescein diacetate-based cell viability tests, for immunocytochemical assays of types I and II collagen, actin and vinculin, for scanning electronic microscopic analysis of cell morphology and distribution, and for gene expression assays of Sox9, aggrecan, procollagen α1(II), procollagen α1(X), and procollagen α2(I) using quantitative RT-PCR assays. After two weeks of culture, the bovine primary chondrocytes had attached on both patterned PP and PS, while practically no adhesion was observed on smooth PP. However, the best adhesion of the cells was on smooth PS. The cells, which attached on patterned PP and PS surfaces synthesized types I and II collagen. The chondrocytes' morphology was extended, and an abundant ECM network formed around the attached chondrocytes on both patterned PP and PS. Upon passaging, no significant differences on the chondrocyte-specific gene expression were observed, although the highest expression level of aggrecan was observed on the patterned PS in passage 1 chondrocytes, and the expression level of procollagen α1(II) appeared to decrease in passaged chondrocytes. However, the expressions of procollagen α2(I) were increased in all passaged cell cultures. In conclusion, the bovine primary chondrocytes could be grown on patterned PS and PP surfaces, and they produced extracellular matrix network around the adhered cells. However, neither the patterned PS nor PP could prevent the dedifferentiation of chondrocytes.

  • 33.
    Prittinen, Juha O.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Ylärinne, Janne H.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Piltti, Juha
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Effect of gravitational force and hydrostatic pressure on the development of articular neocartilage2017In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 25, p. S386-S386Article in journal (Other academic)
  • 34.
    Prittinen, Juha
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Ylärinne, Janne
    Piltti, Juha
    Karhula, Sakari
    Rieppo, Lassi
    Ojanen, Simo
    Korhonen, Rami
    Saarakkala, Simo
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Effect of gravitational force on the development of articular neocartilage with bovine primary chondrocytesManuscript (preprint) (Other academic)
    Abstract [en]

    A lot of effort has been invested into understanding how to assemble cartilage tissue in vitro. Various scaffold types have been used in order to manufacture cartilage tissue with native-like biological properties, while cell-based self-assembly of cartilage without a scaffold material is another strategy utilized. Mechanical forces have also been exploited in the manufacturing process. In this study, we used bovine primary chondrocytes to self-assemble a scaffold-free constructs to investigate whether mechanical loading by gravitational force would be useful in manufacturing cartilage tissue in vitro. Six million chondrocytes were laid on top of defatted bone disks placed inside agarose well in 50 ml culture tubes. The constructs were centrifuged once or three times a day for 15 min at gravitational force of 770 x g for one, two and four weeks. Control samples were cultured under the same conditions without exposure to centrifugation. The samples were analysed by (immuno)histochemistry, Fourier transform infrared imaging, micro-computed tomography, biochemical and gene expression analyses. Biomechanical testing was also performed. Macroscopically, the centrifuged tissues had a more even surface covering a larger area of the bone disk. Fourier transform infrared imaging analysis indicated higher concentration of collagen in the top and bottom edges of the centrifuged samples. Glycosaminoglycan contents increased along the culture, while collagen content appeared to remain at a rather constant level. Aggrecan and procollagen α1(II) gene expression levels had no significant differences, while procollagen α2(I) levels were increased significantly. Biomechanical analyses did not reveal remarkable changes. In conclusion, both of the centrifugation regimes lead to a more uniform tissue constructs, while the biological properties of the native tissue could not be obtained.

  • 35.
    Prittinen, Juha
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Ylärinne, Janne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Piltti, Juha
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Nordlab Kokkola, Keski-Pohjanmaa Central Hospital Soite, Kokkola, Finland.
    Karhula, Sakari S.
    Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland; Infotech Doctoral Program, University of Oulu, Oulu, Finland.
    Rieppo, Lassi
    Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
    Ojanen, S. P.
    Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland; Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Korhonen, Rami K.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Saarakkala, S.
    Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an Jiaotong University, Xi'an, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Effect of centrifugal force on the development of articular neocartilage with bovine primary chondrocytes2019In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 375, no 3, p. 629-639Article in journal (Refereed)
    Abstract [en]

    A lot has been invested into understanding how to assemble cartilage tissue in vitro and various designs have been developed to manufacture cartilage tissue with native-like biological properties. So far, no satisfactory design has been presented. Bovine primary chondrocytes are used to self-assemble scaffold-free constructs to investigate whether mechanical loading by centrifugal force would be useful in manufacturing cartilage tissue in vitro. Six million chondrocytes were laid on top of defatted bone disks placed inside an agarose well in 50-ml culture tubes. The constructs were centrifuged once or three times per day for 15 min at a centrifugal force of 771×g for up to 4 weeks. Control samples were cultured under the same conditions without exposure to centrifugation. The samples were analysed by (immuno)histochemistry, Fourier transform infrared imaging, micro-computed tomography, biochemical and gene expression analyses. Biomechanical testing was also performed. The centrifuged tissues had a more even surface covering a larger area of the bone disk. Fourier transform infrared imaging analysis indicated a higher concentration of collagen in the top and bottom edges in some of the centrifuged samples. Glycosaminoglycan contents increased along the culture, while collagen content remained at a rather constant level. Aggrecan and procollagen α1(II) gene expression levels had no significant differences, while procollagen α2(I) levels were increased significantly. Biomechanical analyses did not reveal remarkable changes. The centrifugation regimes lead to more uniform tissue constructs, whereas improved biological properties of the native tissue could not be obtained by centrifugation.

    Download full text (pdf)
    fulltext
  • 36.
    Qu, Chengjuan
    Department of Biomedicine, Anatomy, University of Kuopio, Kuopio, Finland.
    Articular cartilage proteoglycan biosynthesis and sulfation2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Glucosamine (GlcN) and glucosamine sulfate (GS) have been used to treat the patients with osteoarthritis(OA) as a disease-modifying agent. Previousin vitro studies have focused on the effects of GlcN or GSon cartilage metabolism, whereas in vivo studies have investigated their potential for the treatment of OA. Although these results have raised promises of the disease-modifying effects of GlcN or GS, the cellular mechanisms behind these proposed effects are not clear. In general, the effectiveness of GS in thetreatment of OA as a symptomatic and as a disease-modifying agent is a matter of debate. Loss of proteoglycans (PGs) in OA could be partly due to deficient water binding e.g., by undersulfation of glycosaminoglycans (GAGs). In this study, the molar ratios of chondroitin sulfate (CS)disaccharide isoforms were analyzed with fluorophore-assisted carbohydrate electrophoresis to investigate the hypothesis that sulfate deficiency is involved with the development of bovine and human OA. Our present results indicate that the molar ratio of non-sulfated CS disaccharide in human samples was much lower than that detected in bovine samples, and it did not increase in human OA samples. Conversely, this ratio significantly decreased in bovine OA samples. Furthermore, the steady-state levels of aggrecan mRNA expression and sulfated GAG synthesis were analyzed by using Northern blot assay, quantitative real time reverse transcription polymerase chain reaction and[35S]sulfate incorporation analyses in bovine primary chondrocyte cultures. Aggrecan which is a large CS-PG of cartilage provides osmotic resistance for the cartilage helping it to absorb the compressive loads. Loss of PGs is a major cause of joint dysfunction and disability in OA. However, our results from 25 individual animals showed that none of the different forms of hexosamines, nor the GS salt, could stimulate aggrecan mRNA expression or GAG synthesis in bovine primary chondrocytes. Glucosamine is produced intracellularly from endogenous glucose, and is one of the basic sugar structures required for CS synthesis. It is converted to UDP-glucuronic acid (GlcA) and UDP-N-acetylgalactosamine (UDP-GalNAc) before use for the synthesis of CS polysaccharide chain. If exogenous GS is made available to the cultured cells, it can be directly incorporated into the CS synthesis by UDP-GalNAc via GlcN-6-phosphate bypassing fructose-6-phosphate. Thus, the levels of intracellular UDP-N-acetylhexosamines and UDP-GlcA were explored with reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry in bovine primary chondrocytes to analyze whether a physiologically attainable level of GS could stimulate CS synthesis by increasing intracellular UDP-sugar levels. Our present results with the cells from nine individual animals did not support this hypothesis. In conclusion, bovine and human articular cartilage PGs were not undersulfated in the early stage of OA. Exogenous GS did not increase steady state levels of aggrecan mRNA expression, GAG synthesis or intracellular levels of nucleotide-activated precursors of GAG synthesis in bovine primary chondrocytes.

  • 37.
    Qu, Chengjuan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Brohlin, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Division of Clinical Immunology and Transfusion Medicine, Tissue Establishment, Cell Therapy Unit, Department of Laboratory Medicine, Umeå University Hospital, Umeå, Sweden.
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Evaluation of growth, stemness, and angiogenic properties of dental pulp stem cells cultured in cGMP xeno-/serum-free medium2020In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 380, p. 93-105Article in journal (Refereed)
    Abstract [en]

    This study was aimed to investigate the effects of cGMP xeno-/serum-free medium (XSF, Irvine Scientific) on the properties of human dental pulp stem cells (DPSCs). DPSCs, from passage 2, were cultured in XSF or fetal bovine serum (FBS)-supplemented medium, and sub-cultured up to passage 8. Cumulative population doublings (PDs) and the number of colony-forming-units (CFUs) were determined. qRT-PCR, ELISA, and in vitro assays were used to assess angiogenic capacity. Flow cytometry was used to measure CD73, CD90, and CD105 expression. Differentiation into osteo-, adipo-, and chondrogenic cell lineages was performed. DPSCs showed more elongated morphology, a reduced rate of proliferation at later passages, and lower CFU counts in XSF compared with FBS. Expression of angiogenic factors at the gene and protein levels varied in the two media and with passage number, but cells grown in XSF had more in vitro angiogenic activity. The majority of early and late passage DPSCs cultured in XSF expressed CD73 and CD90. In contrast, the percentage of CD105 positive DPSCs in XSF medium was significantly lower with increased passage whereas the majority of cells cultured in FBS were CD105 positive. Switching XSF-cultured DPSCs to medium supplemented with human serum restored the expression of CD105. The tri-lineage differentiation of DPSCs cultured under XSF and FBS conditions was similar. We showed that despite reduced CD105 expression levels, DPSCs expanded in XSF medium maintained a functional MSC phenotype. Furthermore, restoration of CD105 expression is likely to occur upon in vivo transplantation, when cells are exposed to human serum.

    Download full text (pdf)
    fulltext
  • 38.
    Qu, Chengjuan
    et al.
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Hirviniemi, Mikko
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Töyräs, Juha
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland; Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Effects of freeze-thaw cycle with and without proteolysis inhibitors and cryopreservant on the biochemical and biomechanical properties of articular cartilage2014In: Cartilage, ISSN 1947-6035, E-ISSN 1947-6043, Vol. 5, no 2, p. 97-106, article id 26069689Article in journal (Refereed)
    Abstract [en]

    Objective: We investigated the effects of freeze-thawing on the properties of articular cartilage. Design: The reproducibility of repeated biomechanical assay of the same osteochondral sample was first verified with 11 patellar plugs from 3 animals. Then, 4 osteochondral samples from 15 bovine patellae were divided into 4 groups. The reference samples were immersed in phosphate-buffered saline (PBS) containing proteolysis inhibitors and biomechanically tested before storage for further analyses. Samples of group 1 were biomechanically tested before and after freeze-thawing in PBS in the absence and those of group 2 in the presence of inhibitors. Samples of the group 3 were biomechanically tested in PBS-containing inhibitors, but frozen in 30% dimethyl sulfoxide/PBS and subsequently tested in PBS supplemented with the inhibitors. Glycosaminoglycan contents of the samples and immersion solutions were analyzed, and proteoglycan structures examined with SDS-agarose gel electrophoresis. Results: Freeze-thawing decreased slightly dynamic moduli in all 3 groups. The glycosaminoglycan contents and proteoglycan structures of the cartilage were similar in all experimental groups. Occasionally, the diffused proteoglycans were partly degraded in group 1. Digital densitometry revealed similar staining intensities for the glycosaminoglycans in all groups. Use of cryopreservant had no marked effect on the glycosaminoglycan loss during freeze-thawing. Conclusion: The freeze-thawed cartilage samples appear suitable for the biochemical and biomechanical studies.

  • 39.
    Qu, Cheng-Juan
    et al.
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Jauhiainen, Marjo
    Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland.
    Auriola, Seppo
    Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Effects of glucosamine sulfate on intracellular UDP-hexosamine and UDP-glucuronic acid levels in bovine primary chondrocytes.2007In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 15, no 7, p. 773-779, article id 17320421Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To analyze the effects of exogenously added glucose (Glc), glucosamine (GlcN) and glucosamine sulfate (GS) on the intracellular UDP-hexoses (UDP-Hex), UDP-N-acetylhexosamines (UDP-HexN) and UDP-glucuronic acid (UDP-GlcA) levels in bovine primary chondrocytes.

    METHODS: Chondrocytes were incubated with different concentrations of Glc, GlcN and GS either in high- or low-glucose DMEM for up to 120min to analyze the intracellular levels of UDP-Hex, UDP-GlcA and UDP-HexN by a reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry analysis. Glycosaminoglycan (GAG) synthesis rate and aggrecan mRNA expression levels were quantified using (35)S-sulfate incorporation assay and quantitative real-time RT-PCR, respectively. The cells were cultivated for 2 days or 8 days before UDP-sugar analysis.

    RESULTS: Levels of UDP-HexN and UDP-GlcA were unchanged at 10microM concentration of GS in low-glucose DMEM, while addition of 1mM GlcN or GS in low-glucose DMEM for 10min increased UDP-HexN level. The highest intracellular level of UDP-HexN was reached at 30min after addition of 1mM GS to the cells. The intracellular contents of UDP-HexN and UDP-GlcA related to UDP-Hex were higher after prolonged cultivation of chondrocytes for 8 days compared with 2-day-old cultures. Aggrecan mRNA expression and GAG synthesis remained at control level after the cells were treated with 10, 100microM or 1mM of GS for 24h.

    CONCLUSION: Physiologically relevant level of GS could not increase the intracellular UDP-HexN and UDP-GlcA levels in bovine primary chondrocyte, while longer-time culture itself appeared to increase the intracellular UDP-HexN and UDP-GlcA levels.

  • 40.
    Qu, Chengjuan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, Finland.
    Kaitainen, Salla
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Kröger, Heikki
    Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, Finland.
    Lappalainen, Reijo
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health of Health Science Center, Xi’an Jiaotong University, Xi’an, China.
    Behavior of human bone marrow-derived mesenchymal stem cells on various titanium-based coatings2016In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 9, no 10, article id 827Article in journal (Refereed)
    Abstract [en]

    The chemical composition and texture of titanium coatings can influence the growth characteristics of the adhered cells. An enhanced proliferation of the human mesenchymal stem cells (hMSCs) would be beneficial. The present study was aimed to investigate whether titanium deposited at different atmospheres would affect the cell growth properties, cellular morphology, and expression of surface markers of hMSCs. Titanium-based coatings were deposited on silicon wafers under oxygen, nitrogen, or argon atmospheres by ultra-short pulsed laser deposition using two different gas pressures followed by heating at 400 °C for 2 h. The characteristics of the coated surfaces were determined via contact angle, zeta potential, and scanning electron microscopy (SEM) techniques. Human MSCs were cultivated on differently coated silicon wafers for 48 h. Subsequently, the cell proliferation rates were analyzed with an MTT assay. The phenotype of hMSCs was checked via immunocytochemical stainings of MSC-associated markers CD73, CD90, and CD105, and the adhesion, spreading, and morphology of hMSCs on coated materials via SEM. The cell proliferation rates of the hMSCs were similar on all coated silicon wafers. The hMSCs retained the MSC phenotype by expressing MSC-associated markers and fibroblast-like morphology with cellular projections. Furthermore, no significant differences could be found in the size of the cells when cultured on all various coated surfaces. In conclusion, despite certain differences in the contact angles and the zeta potentials of various titanium-based coatings, no single coating markedly improved the growth characteristics of hMSCs.

    Download full text (pdf)
    fulltext
  • 41.
    Qu, Cheng-Juan
    et al.
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Karjalainen, Hannu
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    The lack of effect of glucosamine sulphate on aggrecan mRNA expression and (35)S-sulphate incorporation in bovine primary chondrocytes.2006In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1762, no 4, p. 453-459, article id 16504489Article in journal (Refereed)
    Abstract [en]

    Glucosamine and glucosamine sulphate have been promoted as a disease-modifying agent to improve the clinical symptoms of osteoarthritis. The precise mechanism of the action of the suggested positive effect of glucosamine or glucosamine sulphate on cartilage proteoglycans is not known, since the level of glucosamine in plasma remains very low after oral administration of glucosamine sulphate. We examined whether exogenous hexosamines or their sulphated forms would increase steady-state levels of aggrecan and hyaluronan synthase (HAS) or glycosaminoglycan synthesis using Northern blot and (35)S-sulphate incorporation analyses. Total RNA was extracted from bovine primary chondrocytes which were cultured either in 1 mM concentration of glucosamine, galactosamine, mannosamine, glucosamine 3-sulphate, glucosamine 6-sulphate or galactosamine 6-sulphate for 0, 4, 8 and 24 h, or in three different concentrations (control, 100 microM and 1 mM) of glucosamine sulphate salt or glucose for 24 or 72 h. Northern blot assay showed that neither hexosamines nor glucosamine sulphate salt stimulated aggrecan and HAS-2 mRNA expression. Glycosaminoglycan synthesis remained at a control level in the treated cultures, with the exception of mannosamine which inhibited (35)S-sulphate incorporation in low-glucose DMEM treatment. In our culture conditions, hexosamines or their sulphated forms did not increase aggrecan expression or (35)S-sulphate incorporation.

  • 42.
    Qu, Chengjuan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of PR China, Xi'an, China.
    Chondrocyte-specific gene expressions in human embryonic stem cells differentiated under feeder-free culture conditions2017In: Current Regenerative Medicine, ISSN 2468-4244, Vol. 7, p. 54-63Article in journal (Refereed)
    Abstract [en]

    Background: Chondrogenic differentiation of human embryonic stem cells (hESCs) has been investigated by maintenance of 3-dimensional cultures in the presence of various exogenous growth factors added during defined stages of culture, or in cocultures with primary chondrocytes, which makes the cultivation process rather complex. Thus, there is a need for easier and more handy expansion and differentiation protocols.

    Objective: The present study is aimed to investigate the potential of hESCs for chondrogenic differentiation in simpler culture conditions.

    Methods: The hESCs were directly cultured for 3 weeks on feeder-free gelatin-coated plates in chondrocyte culture medium without any growth factor supplements after 6-day culture on feeder-free gelatin-coated plate with conditioned medium.

    Results: Immunocytochemical and gene expression analyses indicated that these human directly differentiated cells (hDDCs), which derived from the hESCs, abundantly expressed Sox9, aggrecan, and procollagen a1(II) mRNAs. Upon further passaging, the hDDCs behaved similarly to primary chondrocytes, although the aggrecan mRNA expressions were maintained at a relatively constant level throughout passaging. The procollagen a1(II) mRNAs expression was high in the beginning of the hDDC culture, but declined upon further passaging, which is typical for the primary chondrocytes. The hDDCs could be easily expanded in the monolayer culture using chondrocyte culture medium. Differentiation assays showed that the hDDCs could be differentiated towards chondrocytes, but not adipocytes or osteoblasts.

    Conclusion: Our data suggests that the chondrogenic gene expression could be induced in the directly differentiated hESCs without a need for chondrocyte coculture. In contrast, no osteogenic or adipogenic differentiation was observed.

  • 43.
    Qu, Chengjuan
    et al.
    Department of Biosciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Lindeberg, Heli
    Department of Biosciences, University of Eastern Finland, Kuopio, Finland.
    Ylärinne, Janne
    Department of Biosciences, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Five percent oxygen tension is not beneficial for neocartilage formation in scaffold-free cell cultures2012In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 348, no 1, p. 109-117, article id 22392735Article in journal (Refereed)
    Abstract [en]

    We have investigated whether 5% oxygen tension (O(2)) is beneficial for neocartilage formation when chondrocytes are cultured in transwell-COL inserts. Six million bovine primary chondrocytes were cultured in an insert with DMEM supplemented with 10% fetal bovine serum and antibiotics, with or without glucosamine sulphate (GS) in a 5% or 20% O(2) environment for 2, 4, or 6 weeks. The samples were collected for the histological staining of proteoglycans (PGs) and type II collagen, quantitative reverse transcription with the polymerase chain reaction (RT-PCR) analyses of the mRNA expression of aggrecan and procollagen α(1)(II), procollagen α(2)(I) and hyaluronan synthase 2, quantitation of PGs, and agarose gel electrophoresis. Neocartilage produced at 20% O(2) appeared larger than that at 5% O(2). Histological staining showed that more PGs and type II collagen and better native cartilage structure were produced at 20% than at 5% O(2). The thickness of neocartilage increased during the culture period. Quantitative RT-PCR showed that the procollagen α(1)(II) mRNA expression level was significantly higher at 20% than at 5% O(2). However, no significant difference in gene expression and PG content was found between control and GS-treated cultures at either 20% or 5% O(2). Thus, in contrast to monolayer cultures, engineered cartilage from scaffold-free cultured chondrocytes at 20% O(2) produced better extracellular matrix (ECM) than that at 5% O(2). PGs were mainly large. Exogenous GS was not beneficial for the ECM in scaffold-free chondrocyte cultures.

  • 44.
    Qu, Chengjuan
    et al.
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Myllymaa, Sami
    SIB-Labs, University of Eastern Finland, Kuopio, Finland; Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Prittinen, Juha
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Koistinen, Arto
    SIB-Labs, University of Eastern Finland, Kuopio, Finland.
    Lappalainen, Reijo
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Osteoblast behavior on various ultra short pulsed laser deposited surface coatings2013In: Materials Science and Engineering: C. Materials for Biological Applications, ISSN 0928-4931, Vol. 33, no 3, p. 1676-1682Article in journal (Refereed)
    Abstract [en]

    Ultra short pulsed laser deposition technique was utilized to create amorphous diamond, alumina and carbon nitride, and two different titania coatings on silicon wafers, thus producing five different surface deposited films with variable physico-chemical properties. The surface characterizations, including the roughness, the contact angle and the zeta potential measurements were performed before we tested the growth properties of human osteoblast-like Saos-2 cells on these surfaces (three separate experiments). The average roughness and hydrophobicity were the highest on titania-deposited surfaces, while carbon nitride was the most hydrophilic one. Osteoblasts on all surfaces showed a flattened, spread-out morphology, although on amorphous diamond the cell shape appeared more elongated than on the other surfaces. On rough titania, the area covered by the osteoblasts was smaller than on the other ones. Cell proliferation assay did not show any statistically significant differences.

  • 45.
    Qu, Chengjuan
    et al.
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland;Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Puttonen, Katja
    Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Lindeberg, Heli
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Ruponen, Marika
    Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Hovatta, Outi
    Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
    Koistinaho, Jari
    Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland; Department of Oncology, Kuopio University Hospital, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Chondrogenic differentiation of human pluripotent stem cells in chondrocyte co-culture2013In: International Journal of Biochemistry and Cell Biology, ISSN 1357-2725, E-ISSN 1878-5875, Vol. 45, no 8, p. 1802-1812Article in journal (Refereed)
    Abstract [en]

    Chondrogenic differentiation of human embryonic (hESCs) or induced pluripotent stem cells (hiPSCs) has been achieved in embryoid bodies (EBs) by adding selected growth factors to the medium. Also chondrocyte-secreted factors have been considered to promote the chondrogenic differentiation. Hence, we studied whether co-culture with primary chondrocytes can induce hESCs or hiPSCs to differentiate into chondrocyte lineage. Co-culture of hESCs or hiPSCs was established in a transwell insert system in feeder-free culture conditions, while hESCs or hiPSCs grown alone in the wells were used as controls. After 3-week co-culture with weekly replenished chondrocytes, the chondrogenically committed cells (hCCCs) were evaluated by morphology, immunocytochemistry, quantitative real-time RT-PCR, and analysis of chondrogenic, osteogenic and adipogenic differentiation markers. The expressions of chondrocyte- and pluripotency-associated genes were frequently measured during the monolayer expansion of hCCCs from passage 1 to 10. Human CCCs displayed morphology similar to chondrocytes, and expressed chondrocyte-associated genes, which were declined following passaging, similarly to passaged chondrocytes. They also formed a chondrogenic cell pellet, and differentiated into chondrocytic cells, which secreted abundant extracellular matrix. Human CCCs also proliferated rapidly. However, they did not show osteogenic or adipogenic differentiation capacity. Our results show that co-culture of hESCs or hiPSCs with primary chondrocytes could induce specific chondrogenic differentiation.

  • 46.
    Qu, Cheng-Juan
    et al.
    Department of Biomedicine, Anatomy, University of Kuopio, Kuopio, Finland; Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Pöytäkangas, Teemu
    Department of Biomedicine, Anatomy, University of Kuopio, Kuopio, Finland.
    Jauhiainen, Marjo
    Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland.
    Auriola, Seppo
    Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Glucosamine sulphate does not increase extracellular matrix production at low oxygen tension.2009In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 337, no 1, p. 103-111, article id 19440735Article in journal (Refereed)
    Abstract [en]

    Low oxygen tension may change the dependence of chondrocytes on exogenous carbohydrate sources. In this study, we have investigated whether glucosamine sulphate (GS) stimulates proteoglycan synthesis, the mRNA expression of aggrecan and of type II collagen, and UDP-sugar levels in bovine primary chondrocytes under a low oxygen (O(2)) atmosphere. Chondrocytes from bovine femoral condyles were cultivated with or without GS or sulphate at various concentrations in low- (5.5 mM) or high-glucose (25 mM) DMEM under either a 5% or 20% O(2) atmosphere for 2 or 8 days after isolation. The mRNA expression of aggrecan and type II collagen and the synthesis of glycosaminoglycan (GAG) were determined by quantitative real-time reverse transcription with polymerase chain reaction and a [(35)S]-sulphate incorporation assay, respectively. Aggrecan promoter activity was analysed by a dual-luciferase reporter gene assay. Intracellular UDP-N-acetylhexosamines (UDP-HexN), UDP-glucuronic acid and UDP-hexoses were analysed by reversed-phase high-performance liquid chromatography electrospray ionization mass spectrometry. A low (5%) O(2) atmosphere significantly increased GAG synthesis, mRNA expression of aggrecan and of type II collagen and aggrecan promoter activity in bovine primary chondrocytes. A high (1 mM) concentration of GS was required to increase the level of UDP-HexN. However, GS did not increase GAG synthesis, aggrecan promoter activity or mRNA expression of aggrecan and of type II collagen. Interestingly, a 5% O(2) atmosphere increased the level of UDP-HexN in 8-day cultures without GS treatment. Thus, exogenous GS does not change chondrocyte metabolism, whereas a 5% O(2) atmosphere stimulates extracellular matrix production in bovine primary chondrocytes. The balance of UDP-sugars is changed under a 5% O(2) atmosphere for longer culture periods.

  • 47.
    Qu, Cheng-Juan
    et al.
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Rieppo, Jarno
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Hyttinen, Mika
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Kiviranta, Ilkka
    Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Kurkijärvi, Jatta
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Physics, University of Kuopio, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
    Töyräs, Juha
    Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland.
    Human articular cartilage proteoglycans are not undersulfated in osteoarthritis.2007In: Connective Tissue Research, ISSN 0300-8207, E-ISSN 1607-8438, Vol. 48, no 1, p. 27-33Article in journal (Refereed)
    Abstract [en]

    Chondroitin sulfate is the major constituent of cartilage. Inadequate sulfate availability results in the production of undersulfated proteoglycans. In osteoarthritis, there is a net loss of articular cartilage proteoglycans. Theoretically, it is possible that during the progress of disease undersulfated glycosaminoglycans are synthesized producing proteoglycans with poorer biological properties. In this study, we tested whether in early human osteoarthritic articular cartilage (Mankin's score of 2 and 3) or more advanced disease (Mankin's score over 3), there are proteoglycans that contain a higher relative amount of nonsulfated chondroitin disaccharide isomer in their chondroitin sulfate chains by analyzing the molar ratios of chondroitin sulfate disaccharide isoforms with fluorophore-assisted carbohydrate electrophoresis. Our results indicated that the nonsulfated disaccharide of chondroitin sulfate formed in average only 1-2% of the total chondroitin sulfate. More important, the molar ratio of nonsulfated disaccharide did not appear to be increased in the osteoarthritic articular cartilage. We conclude that undersulfation of articular cartilage proteoglycans is not present in the human osteoarthritic joint.

  • 48.
    Qu, Chengjuan
    et al.
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Rilla, Kirsi
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Tammi, Raija
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Tammi, Markku
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Kröger, Heikki
    Department of Orthopaedics and Traumatology, Kuopio University Hospital, Kuopio, Finland; Bone and Cartilage Research Unit, Surgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Extensive CD44-dependent hyaluronan coats on human bone marrow-derived mesenchymal stem cells produced by hyaluronan synthases HAS1, HAS2 and HAS32014In: International Journal of Biochemistry and Cell Biology, ISSN 1357-2725, E-ISSN 1878-5875, Vol. 48, no 3, p. 45-54, article id 24406795Article in journal (Refereed)
    Abstract [en]

    Hyaluronan (HA), a natural extracellular matrix component, has been considered as an important constituent of the stem cell niche, and successfully used as 3D scaffolds for the chondrogenic differentiation of stem cells. However, the expression levels of HA synthases (HAS1, 2 and 3) and the synthesis of HA by stem cells have remained unknown, and were studied here in the human bone marrow-derived mesenchymal stem cells (hMSCs). Nine hMSCs from different donors were cultured as monolayers with MSC culture medium supplemented with FGF-2. The amount of HA secreted into medium was studied by an ELISA-type assay, and HA bound to cell surface by live cell microscopy. The expression of HASs was analyzed by real time RT-PCR and immunostainings. The HA receptor CD44 was studied by immunocytochemistry. An intense HA coat surrounded the plasma membrane and its protrusions in all nine hMSCs. Displacement assay with HA oligosaccharides indicated that HA coat was at least partly dependent on CD44, which showed similar, relatively high expression in all hMSCs. All HAS isoenzymes were detected, HAS1 showing the largest and HAS3 the smallest range of expression levels between the hMSCs. The secretion of HA ranged between 22.5 and 397.4 ng/10,000 cells/24h, and could not be clearly assigned to the mRNA level of a certain HAS, or a combination of the isoenzymes. This suggests that post-transcriptional and post-translational factors were involved in the adjustment of the HA secretion. In conclusion, all hMSCs expressed high levels of HAS1-3, secrete large amounts of HA, and surround themselves with a thick HA coat bound to CD44. The results suggest that hMSC has the potential for autocrine maintenance of the HA niche, important for their stemness.

  • 49. Wang, Liyun
    et al.
    Guo, Xiong
    Yi, Jianhua
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lei, Jian
    Guo, Qingquan
    Han, Jing
    The effects of long-term low selenium diet on the expression of CHST-3, CHST-12 and UST in knee cartilage of growing rats2018In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 50, p. 123-129Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the effect of low selenium diet on rat´s knee cartilage and expression of chondroitin sulfate (CS) sulfated enzymes in articular and epiphyseal-plate cartilage of rats' femur and tibia.

    METHODS: Twenty-four SD rats were randomly divided into two groups with six female and six male in each group: control group (selenium 0.18 mg/kg), and low selenium group (selenium 0.02 mg/kg). After 109 days, the rats were sacrificed. The ultrastructural changes in chondrocytes of rat knee cartilage were observed by transmission electron microscopy (TEM). The morphology and pathology changes of knee cartilage were examined by hematoxylin-eosin (HE) and toluidine blue (TB) staining. The localization and expression of enzymes involved in CS sulfation, including chondroitin 6-O-sulfotransferase 1 (CHST-3), chondroitin 4-O-sulfotransferase 2 (CHST-12) and uronyl 2-O-sulfotransferase (UST) were examined by immunohistochemical staining and semi-quantitative analysis.

    RESULTS: In low selenium group, ultrastructural changes of chondrocytes were observed in articular cartilage of femur (AF), articular cartilage of tibia (AT), epiphyseal-plate cartilage of femur (EF) and epiphyseal-plate cartilage of tibia (ET); however, no significant changes in chondrocytes number were observed in the above AF, AT, EF or ET. Moreover, reduced thickness of cartilage layer in AF, EF and ET was detected along with reduced staining areas of sulfated glycosaminoglycan in EF and ET in low selenium group. In addition, positive staining rate of CHST-3 was lower in AF, AT and EF, while positive staining rates of CHST-12 and UST were lower in AF, AT, EF and ET in low selenium group when compared with control group.

    CONCLUSIONS: Low selenium undermines the ultrastructure of chondrocytes, inhibits the normal development of cartilage and the expression of CS sulfated enzymes.

  • 50.
    Wang, Liyun
    et al.
    School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.; Shenzhen Institute, Xi'an Jiaotong University, Shenzhen, 518057, Guangzhou, People's Republic of China.
    Yin, Jiafeng
    Department of Laboratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China..
    Yang, Bo
    Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lei, Jian
    School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China;.Shenzhen Institute, Xi'an Jiaotong University, Shenzhen, 518057, Guangzhou, People's Republic of China.
    Han, Jing
    School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China; Shenzhen Institute, Xi'an Jiaotong University, Shenzhen, 518057, Guangzhou, People's Republic of China.
    Guo, Xiong
    School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China..
    Serious selenium deficiency in the serum of patients with Kashin-Beck disease and the effect of nano-selenium on their chondrocytes2020In: Biological Trace Element Research, ISSN 0163-4984, E-ISSN 1559-0720, Vol. 194, no 1, p. 96-104Article in journal (Refereed)
    Abstract [en]

    To investigate selenium (Se) concentrations in serum of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and Kashin-Beck disease (KBD), together with the effect of Se supplement (chondroitin sulfate [CS] nano-Se [SeCS]) on CS structure-modifying sulfotransferases in KBD chondrocyte. Fifty serum samples from each group with aged-matched (40-60 years), normal control (N), RA, OA, and KBD (25 males and females, respectively) were collected to determine Se concentrations. Furthermore, the KBD chondrocytes were divided into two groups following the intervention for 24 h: (a) non-treated KBD group and (b) SeCS-treated KBD group (100 ng/mL SeCS). The ultrastructural changes in chondrocytes were observed by transmission electron microscopy (TEM). Live/dead staining was used to observe cell viability. The expression of CS-modifying sulfotransferases including carbohydrate sulfotransferase 12, 13, and 15 (CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction and western blotting analysis after SeCS intervention. The Se concentrations in serum of KBD, OA, and RA patients were lower than those in control. In OA, RA, and control, Se concentrations were higher in male than in female, while it is opposite in KBD. In the cell experiment, cell survival rate and mitochondrial density were increased in SeCS-treated KBD groups. Expressions of CHST-15, or CHST-12, and CHST-15 on the mRNA or protein level were significantly increased. Expression of UST slightly increased on the mRNA level, but no change was visible on the protein level. Se deficiency in serum of RA, OA, and KBD was observed. SeCS supplemented in KBD chondrocytes improved their survival rate, ameliorated their ultrastructure, and increased the expression of CS structure-modifying sulfotransferases.

12 1 - 50 of 59
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf