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  • 1.
    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.

  • 2.
    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.

  • 3.
    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.

  • 4.
    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 studies2017In: Handbook of famine, starvation, and nutrient deprivation: from biology to policy / [ed] Preedy V.R., Patel V.B., Springer, 2017, p. 1-20Chapter 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.

  • 5.
    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.

  • 6.
    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.

  • 7.
    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.

  • 8.
    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.

  • 9.
    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.

  • 10.
    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.

  • 11.
    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.

  • 12.
    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.

  • 13.
    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: 5th International Conference on Biomedical Engineering and Informatics, IEEE Conference Publications , 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

  • 14.
    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.

  • 15.
    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.

  • 16.
    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.

  • 17.
    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.

  • 18.
    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.

  • 19.
    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.

  • 20.
    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.

  • 21.
    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.

  • 22.
    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.

  • 23.
    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.

  • 24.
    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: ISSN 2468-4244, Vol. 7Article 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.

  • 25.
    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.

  • 26.
    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.

  • 27.
    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.

  • 28.
    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.

  • 29.
    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.

  • 30.
    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.

  • 31.
    Wang, Pan
    et al.
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, China; Clinical Laboratory, The First Hospital of Yulin City, Yulin, China.
    Tan, Wuhong
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, China.
    Qu, Chengjuan
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Zhang, Feng
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, China.
    He, Shulan
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, China.
    Zheng, Jingjing
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, China.
    Shan, Hu
    Department of Respiratory Medicine, The Second Affiliated Hospital, Xi’an Jiaotong University Health Science Center, Xi’an, China.
    Su, Xiaohui
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, China.
    Wang, Bin
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, China.
    Guo, Xiong
    Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, China.
    Genome-wide study identifies the regulatory glycosyltransferase genes networks and signaling pathways from Keshan disease2014In: Journal of Health Science, Vol. 2, no 4, p. 165-173Article in journal (Refereed)
    Abstract [en]

    KD (Keshan disease) is an endemic cardiomyopathy occurring only in China. Its pathogenesis is unclear till now. In the study, gene expression profiles of the PBMC (peripheral blood mononuclear cell) derived respectively from KD patients and healthy in KD areas were compared. Total RNA was isolated, amplified, labeled and hybridized to Agilent 4 × 44 K Whole Human Genome Oligonucleotide Microarray. Significant canonical pathways were analyzed by IPA (ingenuity pathway analysis) to identify differently expressed genes and pathways involved in the cardiovascular system development and function. Quantitative RT-PCR was applied tofurther validate our microarray results. Eighty-three up-regulated (ratios ≥ 2.0) and nine down-regulated glycosyltransferase genes (ratios ≤ 0.5) in PBMC in KD patients were detected by significance analysis of microarrays. Two significant canonical pathways from glycosyltransferase gene expression profiles were screened by IPA. The results of qRT-PCR show that four up-regulated (BMP1/7/10 and FGF18) and one down-regulated (BMP2) genes are consistent with those in microarray experiment, confirming the validity of the microarray data. Based on the results of the study, it is suggested that bone morphogenetic proteins and fibroblast growth factors might play an important role in the pathogenesis of KD. This further helps us to understand the pathogenesis of KD, as well as dilated cardiomyopathy

  • 32.
    Wu, Shi-Xun
    et al.
    College of Medicine of Xi'an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an, China; Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, China.
    Wang, Wei-Zhuo
    Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
    Zhang, Feng
    aculty of Public Health, College of Medicine of Xi'an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an, China.
    Wu, Cui-Yan
    aculty of Public Health, College of Medicine of Xi'an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an, China.
    Dennis, Bannel
    aculty of Public Health, College of Medicine of Xi'an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an, China.
    Qu, Cheng-Juan
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Bai, Yi-Dong
    Department of Cellular and Structural Biology, University of Texas Health Sciences Center at San Antonio, San Antonio, USA.
    Guo, Xiong
    College of Medicine of Xi'an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an, China.
    Expression profiles of genes involved in apoptosis and selenium metabolism in articular cartilage of patients with Kashin-Beck osteoarthritis.2014In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 535, no 2, p. 124-130, article id 24316489Article in journal (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD) is a special type of endemic osteoarthritis. It has been suggested that alterations in selenium metabolism and apoptosis play a role in KBD. However, the underlying molecular mechanism remains largely unclear. We performed a microarray analysis using RNA isolated from cartilages of KBD patients and healthy controls, through Significance Analysis of Microarray (SAM) software. Functional gene networks and crucial molecules associated with differentially expressed genes were investigated via Ingenuity Pathway Analysis (IPA) and hub gene analysis. Quantitative real-time PCR was used to check the validation of chip test. We identified 52 up-regulated apoptosis-related genes and 26 down-regulated selenium-related genes between KBD and controls, and these genes associated with the "MYC-mediated apoptosis signaling pathway". We confirmed the results from array studies with quantitative real-time PCR analysis. Our results suggest that abnormal regulation of selenium metabolism and apoptosis through the MYC mediated signaling pathway contributes to the pathogenesis of KBD, but the relationship between apoptosis gene and selenium gene was not found.

  • 33.
    Wu, Xiaofang
    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.
    Yi, Jianhua
    College of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, PR China.
    Wang, Zuyong
    Biomat lab, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Li, Danyang
    College of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, PR China.
    Yu, Fangfang
    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.
    The effects of chondroitin and/or glucosamine on patients with Kashin-Beck disease2016In: Science Insights Medicine, ISSN 2378-8097, Vol. 2016, article id e00019Article, review/survey (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD), an endemic disease, is a special type of osteoarthritis (OA). Nowadays, due to prevention and treatment methods including selenium supplements, changing grains and water source as well as health education, the morbidity of KBD is reduced significantly as compared to that in the 1950s. However, many elderly adult KBD patients are still suffering from the degenerative changes of cartilage, pain, stiffness and deformation of joints, which are quite similar or even more serious than OA. Chondroitin sulfate and glucosamine have been widely used as symptomatic slow-acting drugs for the treatment of OA. Although their therapeutic effects, biochemical data, pharmacokinetics, preclinical studies, safety and economic evaluation have been well investigated in OA, they are not clearly studied in KBD. In this review, we will evaluate the clinical evidence (randomized controlled trials and non-randomized controlled trials), safeties and cost-effectiveness of chondroitin sulfate and glucosamine for the treatment of KBD. Moreover, the therapeutic mechanisms of chondroitin sulfate and glucosamine are also discussed in details.

  • 34.
    Ylärinne, Janne
    et al.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Qu, Chengjuan
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Hypertonic conditions enhance cartilage formation in scaffold-free primary chondrocyte cultures2014In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, ISSN 1432-0878, Vol. 358, no 2, p. 541-550Article in journal (Refereed)
    Abstract [en]

    The potential of hypertonic conditions at in vivo levels to promote cartilage extracellular matrix accumulation in scaffold-free primary chondrocyte cultures was investigated. Six million bovine primary chondrocytes were cultured in transwell inserts in low glucose (LG), high glucose (HG), or hypertonic high glucose (HHG) DMEM supplemented with fetal bovine serum, antibiotics, and ascorbate under 5 % or 20 % O2 tension with and without transforming growth factor (TGF)-β3 for 6 weeks. Samples were collected for histological staining of proteoglycans (PGs) and type II collagen, analysis by quantitative reverse transcription plus the polymerase chain reaction (RT-PCR) of mRNA expression of aggrecan and procollagen α1 (II) and of Sox9 and procollagen α2 (I), and quantitation of PGs and PG separation in agarose gels. Cartilage tissues produced at 20 % O2 tension were larger than those formed at 5 % O2 tension. Compared with LG, the tissues grew to larger sizes in HG or HHG medium. Histological staining showed the strongest PG and type II collagen staining in cartilage generated in HG or HHG medium at 20 % O2 tension. Quantitative RT-PCR results indicated significantly higher expression of procollagen α1 (II) mRNA in cartilage generated in HHG medium at 20 % O2 tension compared with that in the other samples. TGF-β3 supplements in the culture medium provided no advantage for cartilage formation. Thus, HHG medium used at 20 % O2 tension is the most beneficial combination of the tested culture conditions for scaffold-free cartilage production in vitro and should improve cell culture for research into cartilage repair or tissue engineering.

  • 35.
    Ylärinne, Janne
    et al.
    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). 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, P. R. China.
    Scaffold-free approach produces neocartilage tissue of similar quality as the use of HyStem™ and Hydromatrix™ scaffolds2017In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 28, no 4, article id 59Article in journal (Refereed)
    Abstract [en]

    Numerous biomaterials are being considered for cartilage tissue engineering, while scaffold-free systems have also been introduced. Thus, it is important to know do the scaffolds improve the formation of manufactured neocartilages. This study compares scaffold-free cultures to two scaffold-containing ones. Six million bovine primary chondrocytes were embedded in HyStem™ or HydroMatrix™ scaffolds, or suspended in scaffold-free chondrocyte culture medium, and then loaded into agarose gel supported culture well pockets. Neocartilages were grown in the presence of hypertonic high glucose DMEM medium for up to 6 weeks. By the end of culture periods, the formed tissues were analyzed by histological staining for proteoglycans (PGs) and type II collagen, gene expression measurements of aggrecan, Sox9, procollagen α1(II), and procollagen α2(I) were performed using quantitative RT-PCR, and analyses of PG contents and structure were conducted by spectrophotometric and agarose gel electrophoretic methods. Histological stainings showed that the PGs and type II collagen were abundantly present in both the scaffold-free and the scaffold-containing tissues. The PG content gradually increased following the culture period. However, the mRNA expression levels of the cartilage-specific genes of aggrecan, procollagen α1(II) and Sox9 gradually decreased following culture period, while procollagen α2(I) levels increased. After 6-week-cultivations, the PG concentrations in neocartilage tissues manufactured with HyStem™ or HydroMatrix™ scaffolds, and in scaffold-free agarose gel-supported cell cultures, were similar to native cartilage. No obvious benefits could be seen on the extracellular matrix assembly in HyStem™ or HydroMatrix™ scaffolds cultures.

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