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  • 101.
    Jernberg, Johannes
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Preoperative spinal instability in relation to neurological outcome and survival after surgery for metastatic spinal cord compression in patients with prostate cancer2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 102.
    Jin, Zhan-Kui
    et al.
    Department of Orthopaedics, Shaanxi Provincial People's Hospital (the Affiliated Hospital of Xi'an Medical University), Xi'an, China.
    Yang, Ying
    Xi'an Medical University, Xi'an, China.
    Xu, Cui-Xiang
    Center of Shaanxi Provincial Clinical Laboratory, Shaanxi Provincial People's Hospital (the Affiliated Hospital of Xi'an Medical University), Xi'an, China.
    Yang, Bo
    Department of Orthopaedics, Shaanxi Provincial People's Hospital (the Affiliated Hospital of Xi'an Medical University), Xi'an, China.
    Lammi, Mikko
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, China.
    Chang, Yan-Hai
    Department of Orthopaedics, Shaanxi Provincial People's Hospital (the Affiliated Hospital of Xi'an Medical University), Xi'an, China.
    Ling, Ming
    Department of Orthopaedics, Shaanxi Provincial People's Hospital (the Affiliated Hospital of Xi'an Medical University), Xi'an, China.
    Guo, Xiong
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, China.
    Wang, Xiao-Qing
    Department of Orthopaedics, Shaanxi Provincial People's Hospital (the Affiliated Hospital of Xi'an Medical University), Xi'an, China; Xi'an Medical University, Xi'an, China.
    Outcomes of total knee arthroplasty in the adult Kashin-Beck disease with severe osteoarthritis.2019In: International Orthopaedics, ISSN 0341-2695, E-ISSN 1432-5195, Vol. 43, no 2, p. 323-331, article id 29971707Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and the severe knee pain and functional limitations were seriously affecting the quality of life in patients with end-stage KBD. We retrospectively evaluated the clinical outcomes and the quality of life in KBD patients with total knee arthroplasty (TKA).

    METHODS: A total of 22 subjects (25 knees) suffered KBD with severe knee pain and underwent primary TKA. Knee pain was measured by visual analogue scale (VAS), and the knee function was evaluated by Knee Society Clinical Rating System Score (KSS). KBD Quality of Life (KBDQOL) was used to evaluate the quality of life in KBD patients before and after TKA.

    RESULTS: There were no major complications after TKA. The levels of VAS score were obviously deceased in post-operation than that in pre-operation. The levels of KSS score were increased in one year after TKA compared with the pre-operative values, and it maintained a higher level on three years after TKA. The average KBDQOL score level of each domain in pre-operation and one and three years after TKA was increased accordingly. The average scores of physical function, activity limitation, support of society, mental health, and general health in one year after TKA were significantly higher than those in pre-operation.

    CONCLUSIONS: TKA can reduce knee pain, improve knee function, and improve the quality life in KBD patients. KBDQOL questionnaire may be a promising instrument for assessing the quality life in KBD patients.

  • 103.
    Johans, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Study on genetic variation in inflammatory and bone turnover pathways in relation to osteolytic lesions in total hip arthroplasty2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 104.
    Johansson, Hanna
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Lundin-Olsson, Lillemor
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Littbrand, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Rosendahl, Erik
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Toots, Annika
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Cognitive function and walking velocity in people with dementia: a comparison of backward and forward walking2017In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 58, p. 481-486Article in journal (Refereed)
    Abstract [en]

    How forward and backward walking, both central to everyday life, relate to cognition are relatively unexplored in people with dementia. This study aimed to investigate if forward and backward walking velocity respectively, associated with global cognition and executive function in people with dementia, and whether the association differed according to walking aid use or dementia type. Using a cross-sectional design, 161 participants (77% women), a mean Mini-Mental State Examination (MMSE) score of 15, and mean age of 85.5 years and living in nursing homes were included. Self-paced forward walking (FW) and backward walking (BW) velocity over 2.4 m was measured. Global cognitive outcome measurements included MMSE and Alzheimer Disease Assessment Scale - Cognitive subscale (ADAS-Cog). Executive function was measured using Verbal Fluency (VF). In comprehensively adjusted multivariate linear regression analyses, FW was independently associated with VF (p = 0.001), but not MMSE (p = 0.126) or ADAS-Cog (p = 0.818). BW was independently associated with VF (p = 0.043) and MMSE (p = 0.022), but not ADAS-Cog (p = 0.519). Interaction analyses showed that the association between BW velocity and executive function were stronger in participants who walked without a walking aid. No associations differed according to dementia type. In conclusion, executive function appears important to walking velocity, both forward and backward, in people with dementia with mild to moderately severe cognitive impairment. Global cognitive function was associated with backward walking only, perhaps due to it being more challenging. The association between BW velocity and executive function differed according to use of walking aids, which appeared to attenuate the association.

  • 105. Johansson, Helena
    et al.
    Kanis, John A
    Ljunggren, Östen
    Ström, Oskar
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Mellström, Dan
    10-årsrisken för fraktur. Stöd i behandlingen av osteoporos, enligt preliminära svenska riktlinjer.2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 7, p. 336-339Article in journal (Other academic)
    Abstract [sv]

    Risken för fraktur beräknas med FRAX för män och kvinnor, för olika åldrar, för olika BMI och med följande riskvariabler: tidigare osteoporotisk fraktur, höftfraktur hos föräldrar, aktuell rökning, längre tids peroral behandling med kortison någon gång i livet, förekomst av reumatoid artrit, förekomst av andra sjukdomstillstånd som orsakar osteoporos, aktuell alkoholkonsumtion ≥3 enheter och bentäthetsmätning.

    FRAX finns fritt tillgängligt på Internet.

    I denna artikel beskrivs bakgrunden till FRAX och dess användning vid diagnostik och behandling av osteoporos.

  • 106.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Knee joint laxity and kinematics after anterior cruciate ligament rupture: roentgen stereophotogrammetric and clinical evaluation before and after treatment1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Rupture of the anterior cruciate ligament (ACL) increases anterior-posterior (AP) laxity. The treatment aims to reduce or teach the patient to control this instability. Altered kinematics due to absent ligament function may result in knee arthrosis. This study evaluated the clinical and functional results of reconstructive surgery. Roentgen stereophotogrammetry (RSA) was used to analyse the stabilising effect of knee braces, reconstructive surgery and the kinematics of the knee with and without weight-bearing.

    The stability of the knees were assessed in 86 patients with ACL injuries before and/or after reconstructive surgery with the RSA technique and with the KT-1000 arthrometer The KT- 1000 (89 N) recorded smaller side to side differences than the RSA set-up without any correlation between the methods.

    The effect of three different braces on the AP and rotatory laxity was studied on patients with ACL injuries. The ECKO and the modified Lenox Hill reduced the instability with about one third. The SKB had no significant effect. None of the braces decreased the internal rotatory laxity but the Lenox Hill reduced the external rotatory laxity.

    Thirty-two patients with old ACL tears were treated with surgical reconstruction using the over the top technique (OTT) with or without augmentation. A small reduction in AP laxity was observed at the 6 month follow-up, The AP laxity was almost the same two years after as before surgery. No correlation was observed between the stability and knee function.

    Fifty-four patients with old unilateral anterior cruciate ligament injuries were randomised either to the over the top (OTT) or the isometric femoral tunnel position (ISO) at ACL reconstructive surgery. Seven of 24 (ISO) and 9 of 25 (OTT) had "normal" laxity two years after surgery. The patients operated with the ISO technique did not have better subjective knee function, muscle strength, functional performance or knee stability than patients operated with the OTT technique.

    The knee kinematics in patients with chronic unilateral ACL ruptures were examined during active extension in the supine position (13 patients) and during extension and weight-bearing (13 patients). The tibia displaced at an average 1.9 mm more anteriorly and 0.8 mm distally in the injured than in the intact knees during active extension. During extension and weightbearing the tibia was about 2 mm more posteriorly positioned than in the intact knee. The ACL rupture did not affect tibial rotations.

    Conclusions: The RSA recorded larger side to side differences in ACL injured and reconstructed patients than the KT-1000 arthrometer. Some knee braces are able to reduce AP laxity in ACL injured knees. No correlation was observed after surgery between knee laxity and functional scoring or tests. ACL reconstructions with isometric graft position on the femoral side did not offer any advantages compared to the over the top placement. Altered knee kinematics in the ACL injured knees were observed during knee extension with and without weight-bearing.

  • 107.
    Jortikka, Matti
    et al.
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Inkinen, Ritva
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Markku
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Parkkinen, Jyrki
    Department of Pathology, University of Kuopio, Kuopio, Finland.
    Haapala, Jussi
    Department of Surgery, Kuopio University Hospital, Kuopio, Finland.
    Kiviranta, Ilkka
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Immobilisation causes longlasting matrix changes both in the immobilised and contralateral joint cartilage.1997In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 56, no 4, p. 255-261, article id 9165998Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The capacity of articular cartilage matrix to recover during 50 weeks of remobilisation after an atrophy caused by 11 weeks of immobilisation of the knee (stifle) joint in 90 degrees flexion starting at the age of 29 weeks, was studied in young beagle dogs.

    METHODS: Proteoglycan concentration (uronic acid) and synthesis ([35S]sulphate incorporation) were determined in six and three knee joint surface locations, respectively. Proteoglycans extracted from the cartilages were characterised by chemical determinations, gel filtration, and western blotting for chondroitin sulphate epitope 3B3.

    RESULTS: The proteoglycan concentrations that were reduced in all sample sites immediately after the immobilisation, remained 14-28% lower than controls after 50 weeks of remobilisation in the patella, the summit of medial femoral condyle, and the superior femoropatellar surface. In the contralateral joint, there was a 49% increase of proteoglycans in the inferior femoropatellar surface after remobilisation, while a 34% decrease was simultaneously noticed on the summit of the medial femoral condyle. Total proteoglycan synthesis was not significantly changed after immobilisation or 50 weeks' remobilisation in the treated or contralateral joint, compared with age matched controls. The chondroitin 6- to 4- sulphate ratio was reduced by immobilisation both in the radioactively labelled and the total tissue proteoglycans. In the remobilised joint, this ratio was restored in femur, while in tibia it remained at a level lower than controls. Neither immobilisation nor remobilisation induced epitopes recognised by the monoclonal antibody 3B3 on native (undigested) proteoglycans.

    CONCLUSION: These results show that the depletion of proteoglycans observed after 11 weeks of immobilisation was not completely restored in certain surface sites after 50 weeks of remobilisation. The significant changes that developed in the contralateral joint during the remobilisation period give further support to the idea that a permanent alteration of matrix metabolism results even from a temporary modification of loading pattern in immature joints.

  • 108.
    Julkunen, Petro
    et al.
    Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland; Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland.
    Harjula, Terhi
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Iivarinen, Jarkko
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Marjanen, Juho
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Seppänen, Kari
    Department of Biosciences, Laboratory of Chemistry, University of Kuopio, Kuopio, Finland.
    Närhi, Tommi
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Arokoski, Jari
    Department of Physical and Rehabilitation Medicine, Kuopio University Hospitsl, Kuopio, Finland; Institute of Clinical Medicine, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Finland; Biocenter Kuopio, University of Kuopio, Finland.
    Brama, Pieter
    Section of Veterinary Clinical Studies, School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Dublin, Ireland.
    Jurvelin, Jukka
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Biomechanical, biochemical and structural correlations in immature and mature rabbit articular cartilage.2009In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 17, no 12, p. 1628-1638, article id 19615962Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The structure and composition of articular cartilage change during development and growth. These changes lead to alterations in the mechanical properties of cartilage. In the present study, biomechanical, biochemical and structural relationships of articular cartilage during growth and maturation of rabbits are investigated.

    DESIGN: Articular cartilage specimens from the tibial medial plateaus and femoral medial condyles of female New Zealand white rabbits were collected from seven age-groups; 0 days (n=29), 11 days (n=30), 4 weeks (n=30), 6 weeks (n=30), 3 months (n=24), 6 months (n=24) and 18 months (n=19). The samples underwent mechanical testing under creep indentation. From the mechanical response, instantaneous and equilibrium moduli were determined. Biochemical analyses of tissue collagen, hydroxylysylpyridinoline (HP) and pentosidine (PEN) cross-links in full thickness cartilage samples were conducted. Proteoglycans were investigated depth-wise from the tissue sections by measuring the optical density of Safranin-O-stained samples. Furthermore, depth-wise collagen architecture of articular cartilage was analyzed with polarized light microscopy. Finite element analyses of the samples from different age-groups were conducted to reveal tensile and compressive properties of the fibril network and the matrix of articular cartilage, respectively.

    RESULTS: Tissue thickness decreased from approximately 3 to approximately 0.5mm until the age of 3 months, while the instantaneous modulus increased with age prior to peak at 4-6 weeks. A lower equilibrium modulus was observed before 3-month-age, after which the equilibrium modulus continued to increase. Collagen fibril orientation angle and parallelism index were inversely related to the instantaneous modulus, tensile fibril modulus and tissue thickness. Collagen content and cross-linking were positively related to the equilibrium compressive properties of the tissue.

    CONCLUSIONS: During maturation, significant modulation of tissue structure, composition and mechanical properties takes place. Importantly, the present study provides insight into the mechanical, chemical and structural interactions that lead to functional properties of mature articular cartilage.

  • 109.
    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.

  • 110.
    Juto, Hans
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Gärtner Nilsson, Mattis
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Möller, Michael
    Wennergren, David
    Morberg, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Evaluating non-responders of a survey in the Swedish fracture register: no indication of different functional result2017In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 18, article id 278Article in journal (Refereed)
    Abstract [en]

    Background: The Swedish Fracture Register (SFR) currently contains information on more than 190,000 fractures. Patient Reported Outcome Measures (PROMs) are used for monitoring functional results after fracture treatment. One weakness, as in many surveys, is a low response rate. The aim of the current study was to examine if non-responders of a survey in the SFR differ in PROMs scores, how age and gender influence the response rate and reasons for not responding. Methods: Patients with fractures of radius, ulna or humerus between June and August 2013 and registered in the SFR were included in the study. The non-responders to both the pre-injury and the 1-year survey were contacted by phone and reminded to reply. A comparison of the results of both EQ-5D and Short Musculoskeletal Function Assessment (SMFA) could be made between the responders after a phone reminder and the initial responders. The response rate for the register as a whole was extracted in order to identify how age and gender affect the response rate. Results: Three hundred seventeen of the patients included in the study responded initially. After phone reminder another 94 patients answered the pre-injury survey. Two hundred sixty eight responded initially to the 1-year follow-up survey and 42 after phone reminder. No significant difference was identified in the score of the pre-injury survey between initial responders and responders after phone reminder neither in the EQ-5D nor in the Short Musculoskeletal Function Assessment (SMFA). Regarding the 1-year survey, responders after a phone reminder reported a significantly better outcome in crude data of SMFA score. This difference disappeared after controlling for confounding factors through case control matching. The highest response rate to PROMs in the SFR was among females in the age range 60-69 years. Conclusion: This study indicates that both in the preinjury survey as well as in the 1-year survey the non-responders in the SFR report similar function compared to the initial responders. Age and gender of patients affect the response rate of the survey which needs to be taken into consideration in analysis of data from the SFR.

  • 111.
    Juto, Hans
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Möller, Michael
    Wennergren, David
    Edin, Klas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Apelqvist, Ida
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Morberg, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Substantial accuracy of fracture classification in the Swedish Fracture Register: evaluation of AO/OTA-classification in 152 ankle fractures2016In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, no 11, p. 2579-2583Article in journal (Refereed)
    Abstract [en]

    Introduction: Since 2011 the Swedish Fracture Register (SFR) has collected information on fracture epidemiology, treatment and outcome. More than 112 000 fractures, including 11 600 ankle fractures, have been registered so far. The accuracy of the classification is crucial when using the register in future research and quality improvement of care. In this study we examine the degree of accuracy of the AO/ OTA-classification in which ankle fractures are recorded in the SFR.

    Methods: 152 randomly selected ankle fractures registered in the SFR were classified independently by a reference group of three orthopedic surgeons on two occasions. The agreed AO/OTA-classification of the reference group was regarded as the gold standard classification for each case. The originally recorded classification in the SFR was subsequently compared with the classification of the reference group and accuracy calculated.

    Results: The agreement between the classification in the SFR and of the reference group was 74%, corresponding to kappa 0.67, 95% CI (0.58-0.76) for AO/OTA group level. An agreement of 88% equivalent to kappa 0.77, 95% CI (0.67-0.87) was noted for AO/OTA type level. The agreement corresponds to substantial according to Landis and Koch. The kappa value of inter-and intraobserver agreement ranged from 0.67 to 0.93.

    Conclusions: The study results show substantial agreement between classifications made in the SFR and gold standard classification. The finding is equivalent to or higher than in previous studies. Consequently, we conclude that classifications of ankle fractures in the SFR are accurate and valid.

  • 112.
    Juto, Hans
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sunderby Research Unit.
    Nilsson, Helena
    Morberg, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sunderby Research Unit.
    Epidemiology of Adult Ankle Fractures: 1756 cases identified in Norrbotten County during 2009–2013 and classified according to AO/OTA2018In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 19, article id 441Article in journal (Refereed)
    Abstract [en]

    Background: The ankle fracture is one of the most common fractures, increasing in an ageing population, but not generally seen as an osteoporotic fracture. The aim of this study was to examine the relationship between different AO/OTA classes of ankle fractures, age, sex and type of trauma.

    Methods: Ankle fractures, treated at any of the hospitals in Norrbotten County in Sweden between 2009 and 2013, were retrospectively identified and classified according to the AO/OTA-classification system. Information about the trauma mechanism was also obtained.

    Results: In Norrbotten County, 1756 ankle fractures in 1735 patients aged 20 years or older were identified. This gave an incidence in the county of 179 per 100,000 person-years. Of these patients, 34.6% were 65 years or older, 58.4% were women and 68.2% of the trauma leading to a fracture was defined as low-energy. In 1.5% of the cases the fractures were open. Incidences of type B fractures increased substantially with age, from 62 (95% CI 50–77) at 30–39 years of age to 158 (95% CI 131–190) in patients older than 80 years of age per 100,000 person-years. Type B fractures showed a slightly higher proportion of low-energy trauma while type C showed a lower mean age and proportion of women.

    Conclusions: This study shows an incidence of 179 adult ankle fractures annually per 100,000 persons. More than two thirds of the fractures were caused by a low-energy trauma and ankle fractures are more frequent among females. Females generally have an increased incidence during their life, mainly between the ages of 30 and 60. This is in contrast to men who have more of an even distribution throughout their life. Classification according to AO/OTA reveals some heterogeneity among the classes of ankle fractures in age and gender as well as the energy involved in the trauma.

  • 113.
    Kaarniranta, Kai
    et al.
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Holmberg, Carina
    Turku Centre for Biotechnology, University of Turku, Åbo Akademi University, Turku, Finland; Department of Biochemistry and Pharmacy, Åbo Akademi University, Turku, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Eriksson, John
    Turku Centre for Biotechnology, University of Turku, Åbo Akademi University, Turku, Finland.
    Sistonen, Lea
    Turku Centre for Biotechnology, University of Turku, Åbo Akademi University, Turku, Finland; Department of Biology, Åbo Akademi University, Turku, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Primary chondrocytes resist hydrostatic pressure-induced stress while primary synovial cells and fibroblasts show modified Hsp70 response.2001In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 9, no 1, p. 7-13, article id 11178942Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: During joint loading, chondrocytes in the articular cartilage are subjected to gradients of high compressive hydrostatic pressure (HP). In response to diverse chemical or physical stresses, heat shock genes are induced to express heat shock proteins (Hsps). This study sought to examine the role of Hsps in baroresistance in primary bovine chondrocytes and synovial cells, as well as in primary human fibroblasts.

    METHODS: Northern blotting was used to analyze the steady-state levels of hsp70 mRNA in the primary cells exposed to HP or heat stress. Hsp70 protein accumulation was analyzed by Western blotting, and the DNA-binding activity was examined by gel mobility shift assay.

    RESULTS: Primary bovine chondrocytes which have been adapted to live under pressurized conditions showed negligible Hsp70 response upon HP loading, whereas primary bovine synovial cells and human fibroblasts accumulated hsp70 mRNA and protein when subjected to HP. The response was initiated without activation of the heat shock transcription factor 1. Interestingly, pre-conditioning of the barosensitive fibroblasts with HP or heat shock reduced the Hsp70 response, indicating induction of baroresistance.

    CONCLUSION: This study suggests that Hsp70 can play an important role in the early stages of adaptation of cells to HP. Thus, the Hsp70 gene expression upon HP loading may serve as one indicator of the chondrocytic phenotype of the cells. This can be of use in the treatment of cartilage lesions.

  • 114.
    Kadhem, Alaa
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Influence of preoperative comorbidities on mortalityin patients with femoral neck fracturesA retrospective cohort study, based on prospectively collected material of290 hips2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 115. Kadum, B.
    et al.
    Inngul, C.
    Ihrman, R.
    Sjödén, Göran O.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Sayed-Noor, Arkan S.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Higher preoperative sensitivity to pain and pain at rest are associated with worse functional outcome after stemless total shoulder arthroplasty: a prospective cohort study2018In: The Bone & Joint Journal, ISSN 2049-4394, E-ISSN 2049-4408, Vol. 100B, no 4, p. 480-484Article in journal (Refereed)
    Abstract [en]

    Aims: The aims of this study were to investigate any possible relationship between a preoperative sensitivity to pain and the degree of pain at rest and on exertion with postoperative function in patients who underwent stemless total shoulder arthroplasty (TSA). Patients and Methods: In this prospective study, we included 63 patients who underwent stemless TSA and were available for evaluation one year postoperatively. There were 31 women and 32 men; their mean age was 71 years (53 to 89). The pain threshold, which was measured using a Pain Matcher (PM) unit, the degree of pain (visual analogue scale at rest and on exertion, and function using the short version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), were recorded preoperatively, as well as three and 12 months postoperatively. Results: We found an inverse relationship between both the preoperative PM threshold and pain (VAS) at rest and the 12-month postoperative QuickDASH score (Pearson correlation coefficient (r) >= 0.4, p < 0.05). A linear regression analysis showed that the preoperative PM threshold on the affected side and preoperative pain (VAS) at rest were the only factors associated with the QuickDASH score at 12 months. Conclusion: These findings indicate the importance of central sensitization in the restoration of function after TSA. Further studies are required to investigate whether extra analgesia and rehabilitation could influence the outcome in at risk patients.

  • 116.
    Kadum, Bakir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Total Shoulder Arthroplasty: clinical and radiological studies on the implant positioning and fixation2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Shoulder arthroplasty surgery has shown remarkable progress during the last few decades. A number of factors affect postoperative range of motion, pain and prosthetic durability. Among these factors, the length of the lever arm and joint stability is the ones that can be altered by the selected prosthetic component. It is uncertain how much of the normal anatomy needs to be re-established. Stemless prostheses with total reliance on metaphyseal fixation were introduced in France in 2004 (TESS, Zimmer Biomet). The goals were to avoid stem-related complications. Stemless implants have other potential benefits, including the ability to restore shoulder anatomy.

    Study I: This is a prospective cohort study of 49 patients with one of two versions of the TESS prosthesis (anatomical or reverse) with clinical and radiological follow-up ranging from 9–24 months. The TESS prosthesis showed short-term results that were comparable with other shoulder prosthetic systems.

    Study II: This is a prospective comparative non-randomised study of 37 patients (40 shoulders) who underwent TESS reverse shoulder arthroplasty (RSA) with a follow-up ranging from 15–66 months. We found a significant improvement in functional outcome and reduction of pain in both stemmed and stemless groups. Glenoid overhang influenced the occurrence of scapular notching (SN).

    Study III: This is a radiological study showing that CT had a good reliability and reproducibility in estimating LHO.

    Study IV: This is a prospective radiological study of 69 patients (70 shoulders) with primary osteoarthritis (OA) who had undergone stemless total anatomical shoulder arthroplasty (TSA). This study showed that stemless anatomical TSA could be useful in restoring shoulder anatomy.

    Study V: This is a prospective study of 44 patients with OA who had undergone stemless anatomical TSA with a clinical and radiological follow up ranging from 12 – 50 months. Our study showed that LHO reconstruction close to the anatomy of a healthy contralateral shoulder improved shoulder function. Stemless anatomical TSA help to restore LHO. Increasing LHO may have a negative effect on shoulder function at three months but had no effect at 12 months. The main conclusions of this thesis are:

    1. TSA (anatomic and reverse) using stemless humeral components is reliable if bone quality is adequate. The complication rate is comparable with other shoulder prosthetic systems.

    2. Glenoid overhang decreased complications in RSA.

    3. LHO measurement on AP radiographs is less reliable and underestimates the distance when compared with CT.

    4. Stemless TSA could be of help in reconstructing shoulder anatomy.

    5. Shoulder reconstruction close to the anatomy of a healthy contralateral shoulder improves shoulder function.

     

  • 117.
    Kadum, Bakir
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Hassany, Hamid
    Wadsten, Mats
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Sayed-Noor, Arkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Göran, Sjödén
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Geometrical analysis of stemless shoulder arthroplasty: a radiological study of seventy TESS total shoulder prostheses2016In: International Orthopaedics, ISSN 0341-2695, E-ISSN 1432-5195, Vol. 40, no 4, p. 751-758Article in journal (Refereed)
    Abstract [en]

    Purpose The aim of this study was to investigate the ability of a stemless shoulder prosthesis to restore shoulder anatomy in relation to premorbid anatomy. Methods This prospective study was performed between May 2007 and December 2013. The inclusion criteria were patients with primary osteoarthritis (OA) who had undergone stemless total anatomic shoulder arthroplasty. Radiographic measurements were done on anteroposterior X-ray views of the glenohumeral joint. Results Sixty-nine patients (70 shoulders) were included in the study. The mean difference between premorbid centre of rotation (COR) and post-operative COR was 1 ± 2 mm (range −3 to 5.8 mm). The mean difference between premorbid humeral head height (HH) and post-operative HH was −1 ± 3 mm (range −9.7 to 8.5 mm). The mean difference between premorbid neck-shaft angle (NSA) and post-operative NSA was −3 ± 12° (range −26 to 20°). Conclusions Stemless implants could be of help to reconstruct the shoulder anatomy. This study shows that there are some challenges to be addressed when attempting to ensure optimal implant positioning. The critical step is to determine the correct level of bone cut to avoid varus or valgus humeral head inclination and ensure correct head size.

  • 118.
    Kadum, Bakir
    et al.
    Sundsvall Hosp, Dept Orthopaed, S-85186 Sundsvall, Sweden.
    Mafi, Nader
    Sundsvall Hosp, Dept Orthopaed, S-85186 Sundsvall, Sweden.
    Norberg, Sigge
    Sundsvall Hosp, Dept Orthopaed, S-85186 Sundsvall, Sweden.
    Sayed-Noor, Arkan S
    Sundsvall Hosp, Dept Orthopaed, S-85186 Sundsvall, Sweden.
    Results of the Total Evolutive Shoulder System (TESSA(A (R))): a single-centre study of 56 consecutive patients2011In: Archives of Orthopaedic and Trauma Surgery, ISSN 0936-8051, E-ISSN 1434-3916, Vol. 131, no 12, p. 1623-1629Article in journal (Refereed)
    Abstract [en]

    Shoulder arthroplasty surgery has undergone remarkable progress. New concepts like reverse and stemless shoulder prostheses have been widely used. The Total Evolutive Shoulder System (TESSA (R)) is a new innovative system that provides the surgeon with different prosthetic versions. The purpose of the present study was to evaluate our short-term results and complications of the TESS. 56 consecutive patients were operated with one of the two versions of TESS (anatomical or reverse) between October 2007 and December 2009. Preoperative and postoperative evaluation of the function and life quality was achieved by the Quick Disability of the Arm, Shoulder and Hand (DASH) index and EQ-5D self-report questionnaire, respectively. Radiographic follow-up by anteroposterior, axillary and lateral views was done. The anterosuperior approach was used in all cases. We compared the outcome in fracture patients with other categories. 49 patients were available for 9-24 months (mean 14) clinical and radiographic postoperative follow-up. The mean of quick DASH improved from 56 preoperatively to 34 postoperatively (p < 0.001) and EQ-5D from 0.36 preoperatively to 0.73 postoperatively (p < 0.001). The complications were few and we had no radiolucencies or scapular notching during the study period. Fracture patients did worse compared to other categories. TESS prosthesis showed promising short-term results with few complications. The reverse version could be implanted without stem if initial stability was adequate. Long-term follow-up is required to confirm the results of this innovative system in the long run.

  • 119.
    Kadum, Bakir
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sundsvall Teaching Hosp, Dept Orthopaed, Sundsvall, Sweden.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sundsvall Teaching Hosp, Dept Orthopaed, Sundsvall, Sweden.
    Englund, Erling
    Sayed-Noor, Arkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sundsvall Teaching Hosp, Dept Orthopaed, Sundsvall, Sweden.
    Sjöden, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Sundsvall Teaching Hosp, Dept Orthopaed, Sundsvall, Sweden.
    Clinical and radiological outcome of the Total Evolutive Shoulder System (TESSA (R)) reverse shoulder arthroplasty: a prospective comparative non-randomised study2014In: International Orthopaedics, ISSN 0341-2695, E-ISSN 1432-5195, Vol. 38, no 5, p. 1001-1006Article in journal (Refereed)
    Abstract [en]

    Purpose The aims of this study were to assess the function and quality of life after the Total Evolutive Shoulder System (TESS) reverse shoulder arthroplasty (RSA), to evaluate the radiological stability of the stemless version and to address the effect of arm lengthening and scapular notching (SN) on the outcome. Methods This was a prospective comparative non-randomised study. A total of 37 consecutive patients (40 shoulders) underwent TESS RSA between October 2007 and January 2012; 16 were stemless and 26 were stemmed. At a mean follow-up of 39 months (15-66), we evaluated range of motion (ROM), pain and functional outcome with QuickDASH and quality of life with EQ-5D score. Radiologically, component positioning, signs of loosening, SN and arm length difference were documented. Results We found a significant improvement in functional outcome and reduction of pain in both stemmed and stemless groups. No humeral loosening was evident, but there were four glenoid loosenings. In 12 shoulders that developed SN, seven already had scapular bone impression (SBI) evident on initial post-operative radiographs. Glenoid overhang seemed to decrease the risk of SN. Arm lengthening was associated with better EQ-5D but did not influence ROM or functional outcome. Conclusions Reverse shoulder arthroplasty markedly improved shoulder function. SN is of concern in RSA, but proper positioning of the glenoid component may prevent its development.

  • 120.
    Kadum, Bakir
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Wahlström, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Khoschnau, Shwan
    Sjödén, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sayed-Noor, Arkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Association of lateral humeral offset with functional outcome and geometric restoration in stemless total shoulder arthroplasty2016In: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 25, no 10, p. E285-E294Article in journal (Other academic)
    Abstract [en]

    Background: Restoration of shoulder geometry is desirable in total shoulder arthroplasty (TSA) and thought to influence the postoperative clinical outcome. We aimed to study the association of postoperative lateral humeral offset (LHO) changes and clinical outcome, as well as to investigate the ability of stemless anatomic TSA to restore shoulder geometry. Methods: In patients with primary shoulder osteoarthritis who underwent stemless anatomic TSA, the preoperative and postoperative clinical outcome was measured. Shoulder geometry was measured on preoperative computed tomography for the osteoarthritic shoulder and contralateral healthy shoulder and on postoperative computed tomography for the operated shoulder. Results: Forty-four patients with a minimum follow-up of 12 months (range, 12-50 months) were available for the study. Postoperatively, the clinical outcome measures improved. The postoperative difference in LHO between the operated shoulder and contralateral healthy shoulder was 1.3 +/- 4.6 mm and was correlated with scores on the short version of the Disabilities of the Arm, Shoulder and Hand questionnaire at 3 months (Pearson correlation = 0.36, P =.01) and visual analog scale for pain at rest (Pearson correlation = 0.30, P =.03) and with exertion (Pearson correlation = 0.34, P =.01) at 3 months. Lengthening of LHO was associated with worsening shoulder function at 3 months but not at 12 months. The postoperative shoulder geometric parameters were restored postoperatively to acceptable ranges. Conclusion: The stemless anatomic TSA could restore shoulder geometry in an acceptable manner. At 3 months but not at 12 months, increased LHO had a negative effect on shoulder function and resulted in more shoulder pain at rest and with exertion but did not affect quality of life, health status, or range of motion.

  • 121.
    Kallioniemi, Antti
    et al.
    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.
    Nieminen, Miika
    Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland .
    Lammi, Mikko
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland .
    Töyräs, Juha
    Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland.
    Contrast agent enhanced pQCT of articular cartilage.2007In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 52, no 4, p. 1209-1219, article id 17264381Article in journal (Refereed)
    Abstract [en]

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n=3) and trypsin-degraded (n=3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n=16). After trypsin-induced PG loss (-70%, p<0.05) the penetration of gadopentetate and ioxaglate increased (p<0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r=-0.95, r=-0.94, p<0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded articular cartilage in vitro. As high resolution imaging of e.g. the knee joint is possible with pQCT, the present technique may be further developed for in vivo quantification of PG depletion in osteoarthritic cartilage. However, careful in vitro and in vivo characterization of diffusion mechanics and optimal contrast agent concentrations are needed before diagnostic applications are feasible.

  • 122. Karhula, Sakari
    et al.
    Finnilä, Mikko
    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.
    Ylärinne, Janne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kauppinen, Sami
    Rieppo, Lassi
    Pritzker, Kenneth P H
    Nieminen, Heikki
    Saarakkala, Simo
    Effects of articular cartilage constituents on phosphotungstic acid enhanced micro-computed tomography2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0171075Article in journal (Refereed)
    Abstract [en]

    Contrast-enhanced micro-computed tomography (CEμCT) with phosphotungstic acid (PTA) has shown potential for detecting collagen distribution of articular cartilage. However, the selectivity of the PTA staining to articular cartilage constituents remains to be elucidated. The aim of this study was to investigate the dependence of PTA for the collagen content in bovine articular cartilage. Adjacent bovine articular cartilage samples were treated with chondroitinase ABC and collagenase to degrade the proteoglycan and the collagen constituents in articular cartilage, respectively. Enzymatically degraded samples were compared to the untreated samples using CEμCT and reference methods, such as Fourier-transform infrared imaging. Decrease in the X-ray attenuation of PTA in articular cartilage and collagen content was observed in cartilage depth of 0-13% and deeper in tissue after collagen degradation. Increase in the X-ray attenuation of PTA was observed in the cartilage depth of 13-39% after proteoglycan degradation. The X-ray attenuation of PTA-labelled articular cartilage in CEμCT is associated mainly with collagen content but the proteoglycans have a minor effect on the X-ray attenuation of the PTA-labelled articular cartilage. In conclusion, the PTA labeling provides a feasible CEμCT method for 3D characterization of articular cartilage.

  • 123.
    Karis, Emma
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Retrospective evaluation of microbiological diagnosis and clinical outcome in aseptic and septic revision hip arthroplasty2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 124.
    Karppinen, Jaro
    et al.
    Department of Physical Medicine and Rehabilitation, University of Oulu, Oulu, Finland.
    Inkinen, Ritva
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Kääpä, Eeva
    Department of Physical Medicine and Rehabilitation, University of Oulu, Oulu, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Markku
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Holm, Sten
    Department of Orthopaedics, Sahlgren Hospital, University of Göteborg, Göteborg, Sweden.
    Vanharanta, Hannu
    Department of Physical Medicine and Rehabilitation, University of Oulu, Oulu, Finland.
    Effects of tiaprofenic acid and indomethacin on proteoglycans in the degenerating porcine intervertebral disc.1995In: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 20, no 10, p. 1170-1177, article id 7638661Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN: Eighteen pigs were stabbed with a scalpel in the anterior part of the anulus fibrosus of a lumbar disc. After surgery, the pigs received either tiaprofenic acid or indomethacin daily, and a third group did not receive any medication.

    OBJECTIVES: Nonsteroidal anti-inflammatory agents are widely used in the treatment of low back patients, but their long-term effects on the matrix molecules in the degenerate disc are unknown.

    SUMMARY OF BACKGROUND DATA: Several in vitro and in vivo studies on articular cartilage have suggested that tiaprofenic acid may not have adverse effects on matrix metabolism, whereas indomethacin probably does.

    METHODS: Uronic acid, DNA, and water contents were determined from five different locations in each injured disc. Transport and incorporation of sulfate were examined by in vivo radioactive tracer analysis, and proteoglycan structures were analyzed by gel electrophoresis.

    RESULTS: Morphologically, there were no differences between the treatments. Tiaprofenic acid maintained a higher uronic acid content in the nucleus pulposus and outer anulus compared with that of the nonmedicated animals. Tiaprofenic acid decreased the incorporation of sulfate in the injured area and the water content at most sites. Indomethacin had no adverse effects compared with the nonmedicated group, and it increased water content in the posterior anulus fibrosus.

    CONCLUSIONS: Long-term administration of tiaprofenic acid and indomethacin did not have harmful effects on matrix metabolism after disc injury. On the contrary, tiaprofenic acid may slightly protect proteoglycans in the degenerating disc.

  • 125.
    Karsten, Gustav
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Risk factors for treatment failure of osteosynthesis in undisplaced femoral neck fractures2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 126.
    Kassem, Ali
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Henning, Petra
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Souza, Pedro P. C.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lindholm, Catharina
    Lerner, Ulf H.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Porphyromonas gingivalis Stimulates Bone Resorption by Enhancing RANKL (Receptor Activator of NF-kappa B Ligand) through Activation of Toll-like Receptor 2 in Osteoblasts2015In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 290, no 33, p. 20147-20158Article in journal (Refereed)
    Abstract [en]

    Periodontitis has been associated with rheumatoid arthritis. In experimental arthritis, concomitant periodontitis caused by oral infection with Porphyromonas gingivalis enhances articular bone loss. The aim of this study was to investigate how lipopolysaccharide (LPS) from P. gingivalis stimulates bone resorption. The effects by LPS P. gingivalis and four other TLR2 ligands on bone resorption, osteoclast formation, and gene expression in wild type and Tlr2-deficient mice were assessed in ex vivo cultures of mouse parietal bones and in an in vivo model in which TLR2 agonists were injected subcutaneously over the skull bones. LPS P. gingivalis stimulated mineral release and matrix degradation in the parietal bone organ cultures by increasing differentiation and formation of mature osteoclasts, a response dependent on increased RANKL (receptor activator of NF-kappa B ligand). LPS P. gingivalis stimulated RANKL in parietal osteoblasts dependent on the presence of TLR2 and through a MyD88 and NF-kappa B-mediated mechanism. Similarly, the TLR2 agonists HKLM, FSL1, Pam2, and Pam3 stimulated RANKL in osteoblasts and parietal bone resorption. LPS P. gingivalis and Pam2 robustly enhanced osteoclast formation in periosteal/endosteal cell cultures by increasing RANKL. LPS P. gingivalis and Pam2 also up-regulated RANKL and osteoclastic genes in vivo, resulting in an increased number of periosteal osteoclasts and immense bone loss in wild type mice but not in Tlr2-deficient mice. These data demonstrate that LPS P. gingivalis stimulates periosteal osteoclast formation and bone resorption by stimulating RANKL in osteoblasts via TLR2. This effect might be important for periodontal bone loss and for the enhanced bone loss seen in rheumatoid arthritis patients with concomitant periodontal disease.

  • 127. Kerje, Susanne
    et al.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Do, Lan
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Larsson, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kämpe, Olle
    Engström-Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Ulla
    Is low molecular hyaluronan an early indicator of disease in avian systemic sclerosis?2016In: Connective Tissue Research, ISSN 0300-8207, E-ISSN 1607-8438, Vol. 57, no 5, p. 337-346Article in journal (Refereed)
    Abstract [en]

    AIM OF THE STUDY: To further elucidate the pathogenesis of systemic sclerosis (SSc) an experimental avian model was used. University of California at Davies line 200-chicken (UCD-200) spontaneously develops a SSc like disease that has most features of human SSc with vascular effects, inflammation, autoimmunity and fibrosis. The first signs of disease in UCD-200 are swelling and ischemic lesions of the comb, a tissue containing high amounts of the glycosaminoglycan hyaluronan. The aim was to evaluate inflammatory and fibrotic processes of the disease with regard to the molecular weight of hyaluronan.

    MATERIAL AND METHODS: Comb biopsies from UCD-200 and healthy White Leghorn (WL) chickens as controls at different ages were studied with histochemical localization of hyaluronan, hyaluronidase 1, CD3, IgY and collagen I and III. Hyaluronan molecular weight distribution was estimated with gas phase electrophoretic analysis.

    RESULTS: At 2 days of age hyaluronan was visualized in UCD-200 at the dermal part of the comb with no simultaneous staining of Hyal-1. In adult UCD-200 the comb skin was almost totally devoid of hyaluronan compared to WL of the same age. An increase of low molecular weight (LMW) hyaluronan was detected in comb tissue from UCD-200 at 1 day, 1, 2, 4 weeks in contrast to adult animals.

    CONCLUSIONS: An early inflammatory process involving LMW hyaluronan was confirmed as a possible profibrotic process. This indicates that hyaluronan might be an important participant in early inflammatory events of SSc in UCD-200 chicken and that disappearance of hyaluronan in skin predisposes to fibrosis.

  • 128.
    Kinnunen, Jussi
    et al.
    Department of Physics and Mathematics, University of Eastern Finland, Joensuu, Finland.
    Kokkonen, Harri
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Kovanen, Vuokko
    Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
    Hauta-Kasari, Markku
    School of Computing, University of Eastern Finland, Joensuu, Finland.
    Vahimaa, Pasi
    Department of Physics and Mathematics, University of Eastern Finland, Joensuu, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Töyräs, Juha
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Nondestructive fluorescence-based quantification of threose-induced collagen cross-linking in bovine articular cartilage2012In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 17, no 9, p. 97003-, article id 22975679Article in journal (Refereed)
    Abstract [en]

    Extensive collagen cross-linking affects the mechanical competence of articular cartilage: it can make the cartilage stiffer and more brittle. The concentrations of the best known cross-links, pyridinoline and pentosidine, can be accurately determined by destructive high-performance liquid chromatography (HPLC). We explore a nondestructive evaluation of cross-linking by using the intrinsic fluorescence of the intact cartilage. Articular cartilage samples from bovine knee joints were incubated in threose solution for 40 and 100 h to increase the collagen cross-linking. Control samples without threose were also prepared. Excitation-emission matrices at wavelengths of 220 to 950 nm were acquired from the samples, and the pentosidine and pyridinoline cross-links and the collagen concentrations were determined using HPLC. After the threose treatment, pentosidine and lysyl pyridinole (LP) concentrations increased. The intrinsic fluorescence, excited below 350 nm, decreased and was related to pentosidine [r=−0.90, 240/325nm (excitation/emission)] or LP (r=−0.85, 235/285nm) concentrations. Due to overlapping, the changes in emission could not be linked specifically to the recorded cross-links. However, the fluorescence signal enabled a nondestructive optical estimate of changes in the pentosidine and LP cross-linking of intact articular cartilage.

  • 129.
    Király, Kari
    et al.
    Department of Anatomy, University o Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University o Kuopio, Kuopio, Finland.
    Arokoski, Jari
    Department of Anatomy, University o Kuopio, Kuopio, Finland.
    Lapveteläinen, Tuomo
    Department of Anatomy, University o Kuopio, Kuopio, Finland.
    Tammi, Markku
    Department of Anatomy, University o Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, University o Kuopio, Kuopio, Finland.
    Kiviranta, Ilkka
    Safranin O reduces loss of glycosaminoglycans from bovine articular cartilage during histological specimen preparation.1996In: The Histochemical Journal, ISSN 0018-2214, E-ISSN 1573-6865, Vol. 28, no 2, p. 99-107, article id 8737291Article in journal (Refereed)
    Abstract [en]

    The ability of Safranin O, added to fixation and decalcification solutions, to prevent the escape of glycosaminoglycans (GAGs) from small cartilage tissue blocks during histological processing of cartilage has been studied. GAGs in the fixatives and decalcifying solutions used and those remaining in the 1 mm3 cubes of cartilage were assayed biochemically. The quantity of GAGs remaining in the cartilage cubes were determined from Safranin O-stained sections using videomicroscopy or microspectrophotometry. A quantity (10.6%) of GAGs were lost during a conventional 4% buffered formaldehyde fixation (48 h) and a subsequent decalcification in 10% EDTA (12 days) at 4 degrees C. Roughly one-quarter of the total GAG loss occurred during the 48 h fixation, and three-quarters during the 12 days of decalcification. Inclusion of 4% formaldehyde in the decalcification fluid decreased the loss of GAGs to 6.2%. The presence of 0.5% Safranin O in the fixative reduced this loss to 3.4%. When 0.5% Safranin O was included in the fixative and 4% formaldehyde in the decalcification solution, Safranin O staining of the histological sections increased on average by 13.5%. After fixation in the presence of 0.5% Safranin O, there was no difference in the staining intensities when decalcification was carried out in the presence of either Safranin O or formaldehyde, or both. It took 24 h for Safranin O to penetrate into the deep zone of articular cartilage, warranting a fixation period of at least this long. In conclusion, the addition of Safranin O to the fixative and either Safranin O or formaldehyde in the following decalcification fluid, markedly reduces the loss of GAGs from small articular cartilage explants during histological processing. However, for immunohistochemical studies, Safranin O cannot be included in the processing solutions, because it may interfere.

  • 130.
    Kiviranta, Ilkka
    et al.
    Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Tammi, Markku
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Arokoski, Jari
    Department of Physical and Rehabilitation Medicine, Kuopio University Hospital, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
    Säämänen, Anna-Marja
    Department of Medical Biochemistry and Molecular Biology, University of Turku, Turku, Finland.
    Parkkinen, Jyrki
    Department of Pathology, University of Kuopio, Kuopio, Finnand.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Hyttinen, Mika
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Effects of mechanical loading and immobilization on the articular cartilage1997In: Bailliere's Clinical Orthopaedics, ISSN 1074-8814, Vol. 2, no 1, p. 109-122Article, review/survey (Refereed)
    Abstract [en]

    Articular cartilage provides nearly frictionless surfaces for joint movemants and reduces contact pressures, protecting the underlying suchondral bone from excess stress. The unique properties of articular cartilage are based on the interaction of the main components of the extracellular matrix: proteoglycans (PGs), collagen and interstitial fluid. Animal experiments and in vitro studies demonstrate that one of the most important regulators of the extracellular matrix metabolism is mechanical loading acting on the joints. Unloading and immobilization leads to PG depletion and softening of articular cartilage, increasing the risk of permanent cartilage degeneration. Moderate running exercise and increased weight bearing increases cartilage thickness, PG concentration and improves biomechanical properties of articular cartilage. With further increase in training intensity this positive influence of exercise disappears and cartilage shows changes analogous to immobilization of the joint, i.e. PG depletion and softening of the tissue. In humans most epidemiological studies  have failed to prove the connection between running training and cartilage degeneration, but there is evidence that sports activities exposing joints to impact loading might increase the risk of osteoarthrosis.

  • 131.
    Knutsson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Mukka, Sebastian
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Wahlström, Jens
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Järvholm, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Sayed-Noor, Arkan S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    The association between tobacco smoking and surgical intervention for lumbar spinal stenosis: cohort study of 331,941 workers2018In: The spine journal, ISSN 1529-9430, E-ISSN 1878-1632, Vol. 18, no 8, p. 1313-1317Article in journal (Refereed)
    Abstract [en]

    BACKGROUND CONTEXT: Tobacco smoking is an injurious habit associated with a number of chronic disorders. Its influence on disc metabolism and degeneration including lumbar spinal stenosis (LSS) has been investigated in the literature.

    PURPOSE: We aimed to investigate whether tobacco smoking is an independent risk factor for undergoing surgical intervention for LSS.

    STUDY DESIGN/SETTING: This is a prospective cohort study.

    PATIENT SAMPLE: The patient sample of 331,941 workers was derived from a Swedish nationwide occupational surveillance program for construction workers.

    OUTCOME MEASURE: The outcome measure included the incidence of undergoing surgical intervention for LSS in tobacco smokers versus no smokers.

    MATERIALS AND METHODS: At inclusion, age, sex, body mass index (BMI), workers' job title, and self-reported smoking habits were registered. The workers were divided into four categories: never smoked, former smoker, moderate current (1-14 cigarettes/day), and heavy current (≥15 cigarettes/day). Patients who underwent a surgically treated LSS were defined using the relevant International Classification of Diseases (ICD) disease code derived from the Swedish National Patient Register.

    RESULTS: A total of 331,941 participants were included in the analysis. Forty-four percent of the participants were non-smokers, 16% were former smokers, 26% were moderate smokers, and 14% were heavy smokers. The vast majority of construction workers were males (95%). During the average follow-up of 30.7 years, 1,623 participants were surgically treated for LSS. The incidence rate ratio (IRRs) of LSS varied across smoking categories, with the highest values found in heavy smokers. Compared with non-smokers, all smoking categories show an increased incidence of surgically treated LSS. The findings were consistent even when the comparison was performed for participants with BMIs between 18.5 and 25 and for participants aged between 40 and 74 years.

    CONCLUSIONS: Tobacco smoking is associated with an increased incidence of surgically treated LSS. The effect seems to be dose related, whereby heavy smokers have a higher risk than moderate or former smokers.

  • 132.
    Kopakkala-Tani, Milla
    et al.
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Leskinen, Jarkko
    Deparment of Physics, University of Kuopio, Kuopio, Finland.
    Karjalainen, Hannu
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Karjalainen, Tero
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Hynynen, Kullervo
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Töyräs, Juha
    Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland.
    Ultrasound stimulates proteoglycan synthesis in bovine primary chondrocytes.2006In: Biorheology, ISSN 0006-355X, E-ISSN 1878-5034, Vol. 43, no 3-4, p. 271-282, article id 16912400Article in journal (Refereed)
    Abstract [en]

    Mechanical forces can stimulate the production of extracellular matrix molecules. We tested the efficacy of ultrasound to increase proteoglycan synthesis in bovine primary chondrocytes. The ultrasound-induced temperature rise was measured and its contribution to the synthesis was investigated using bare heat stimulus. Chondrocytes from five cellular isolations were exposed in triplicate to ultrasound (1 MHz, duty cycle 20%, pulse repetition frequency 1 kHz) at average intensity of 580 mW/cm2 for 10 minutes daily for 1-5 days. Temperature evolution was recorded during the sonication and corresponding temperature history was created using a controllable water bath. This exposure profile was used in 10-minute-long heat treatments of chondrocytes. Heat shock protein 70 (Hsp70) levels after one-time treatment to ultrasound and heat was analyzed by Western blotting, and proteoglycan synthesis was evaluated by 35S-sulfate incorporation. Ultrasound treatment did not induce Hsp70, while heat treatment caused a slight heat stress response. Proteoglycan synthesis was increased approximately 2-fold after 3-4 daily ultrasound stimulations, and remained at that level until day 5 in responsive cell isolates. However, chondrocytes from one donor cell isolation out of five remained non-responsive. Heat treatment alone did not increase proteoglycan synthesis. In conclusion, our study confirms that pulsed ultrasound stimulation can induce proteoglycan synthesis in chondrocytes.

  • 133.
    Kulmala, Katariina
    et al.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Karjalainen, Hannu
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Kokkonen, Harri
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Kovanen, Vuokko
    Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Korhonen, Rami
    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.
    Diffusion of ionic and non-ionic contrast agents in articular cartilage with increased cross-linking: contribution of steric and electrostatic effects2013In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 35, no 10, p. 1415-20Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the effect of threose-induced collagen cross-linking on diffusion of ionic and non-ionic contrast agents in articular cartilage.

    DESIGN: Osteochondral plugs (Ø=6mm) were prepared from bovine patellae and divided into two groups according to the contrast agent to be used in contrast enhanced computed tomography (CECT) imaging: (I) anionic ioxaglate and (II) non-ionic iodixanol. The groups I and II contained 7 and 6 sample pairs, respectively. One of the paired samples served as a reference while the other was treated with threose to induce collagen cross-linking. The equilibrium partitioning of the contrast agents was imaged after 24h of immersion. Fixed charge density (FCD), water content, contents of proteoglycans, total collagen, hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP) and pentosidine (Pent) cross-links were determined as a reference.

    RESULTS: The equilibrium partitioning of ioxaglate (group I) was significantly (p=0.018) lower (-23.4%) in threose-treated than control samples while the equilibrium partitioning of iodixanol (group II) was unaffected by the threose-treatment. FCD in the middle and deep zones of the cartilage (p<0.05) and contents of Pent and LP (p=0.001) increased significantly due to the treatment. However, the proteoglycan concentration was not systematically altered after the treatment. Water content was significantly (-3.5%, p=0.007) lower after the treatment.

    CONCLUSIONS: Since non-ionic iodixanol showed no changes in partition after cross-linking, in contrast to anionic ioxaglate, we conclude that the cross-linking induced changes in charge distribution have greater effect on diffusion compared to the cross-linking induced changes in steric hindrance.

  • 134. Kurmis, Andrew P
    et al.
    Kurmis, Timothy P
    O'Brien, Justin X
    Dalén, Tore
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    The effect of nonsteroidal anti-inflammatory drug administration on acute phase fracture-healing: a review2012In: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 94, no 9, p. 815-823Article in journal (Refereed)
  • 135.
    Kääpä, Eeva
    et al.
    Department of Medical Chemistry, Unversity of Helsinki, Helsinki, Finland.
    Holm, Sten
    Department of Orthopaedics, Sahlgren Hospital, Göteborg, Sweden.
    Inkinen, Ritva
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Markku
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Vanharanta, Hannu
    Department of Physical Medicine and Rehabilitation, University of Oulu, Oulu, Finland.
    Proteoglycan chemistry in experimentally injured porcine intervertebral disk.1994In: Journal of spinal disorders, ISSN 0895-0385, E-ISSN 1531-2305, Vol. 7, no 4, p. 296-306, article id 7949697Article in journal (Refereed)
    Abstract [en]

    An animal model of disk degeneration was used to study the concentration levels and types of proteoglycans in the different parts of the intervertebral disk. An annular incision was made with a scalpel blade into the anterior part of the porcine lumbar intervertebral disks via a retroperitoneal approach. Three months after injury the morphology of the injured disk had changed considerably. Disk height was diminished, and in the injured segment osteophytes had formed at the ventral edges of the vertebral body. The nucleus was small, fibrous, and yellowish. The annular lesion had healed by formation of granulation tissue, but the lamellar structure was partially destroyed. The concentration of inorganic [35S]sulfate had decreased across the whole disk, reflecting a decrease in the rate of solute transport. The concentration of incorporated [35S]sulfate had also decreased in the injured disks. The DNA concentration in the anterior annulus and in the nucleus had increased, whereas both the concentration of uronic acid and the ratio of chondroitin-6-sulfate to chondroitin-4-sulfate in the nucleus had decreased. Agarose gel electrophoresis combined with chondroitinase B digestion suggested the presence of dermatan sulfate proteoglycans in the injured annulus fibrosus. The morphology and chemical composition of the disks adjacent to the injured one were normal, and only a slight increase in the concentration of incorporated [35S]sulfate was observed in the disks above the injured one.

  • 136.
    Kääpä, Eeva
    et al.
    Department of Physical, Medicine and Rehabilitation, Helsinki University Hospital, Helsinki, Finland.
    Wang, Wei
    Department of Biology of Physical Activity, University of Jyväskylä, Finland.
    Takala, Timo
    Department of Biology of Physical Activity, University of Jyväskylä, Finland.
    Poussa, Mikko
    Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland.
    Konttinen, Yrjö
    Fourth Department of Medicine, Helsinki University Hospital, Helsinki, Finland; Department of Biology of Physical Activity, University of Jyväskylä, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Vanharanta, Heikki
    Department of Physical, Medicine and Rehabilitation, Oulu University, Finland.
    Elevated protein content and prolyl 4-hydroxylase activity in severely degenerated human annulus fibrosus.2000In: Connective Tissue Research, ISSN 0300-8207, E-ISSN 1607-8438, Vol. 41, no 2, p. 93-99, article id 10992155Article in journal (Refereed)
    Abstract [en]

    Alterations involved with the intervertebral disc degeneration are partly well described, however, it is not so well known how collagen network is affected by the disease. We analyzed the rate of collagen biosynthesis (estimated by the enzymic activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase) and the level of hydroxylysylpyridinoline and lysylpyridinoline crosslinks both in normal (n=7) and degenerated (n=7) human annulus fibrosus. The activity of prolyl 4-hydroxylase was significantly increased in degenerated tissue. However, no significant changes in the collagen content or in the amount of hydroxylysylpyridinoline and lysylpyridinoline collagen crosslinks were observed. On the other hand, the content of soluble proteins was significantly increased. Our results suggest that collagen biosynthesis is increased in degenerated human annulus fibrosus, obviously to compensate the impairment of collagen fibers. The faster turnover of collagen in degenerated annulus fibrosus, suggested by the increased prolyl 4-hydroxylase activity and unchanged collagen content, seems not to cause any significant changes in its mature pyridinium crosslink concentrations.

  • 137.
    Lammi, Mikko
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Cellular signaling in cartilage tissue engineering2007In: Current Signal Transduction Therapy, ISSN 2212-389X (Online), 1574-3624 (Print), Vol. 2, no 1, p. 41-48Article, review/survey (Refereed)
    Abstract [en]

    Osteoarthritis is a common disease in humans, which is caused by progressive degradation of articular cartilage and imbalance of extracellular matrix turnover. It usually causes pain and malfunction of the affected joints, and the incidence of this disease increases with aging. Classical treatment for osteoarthritis is pain alleviation and, in progressed disease, surgical operations. New surgical techniques include transplantation of autologous chondrocytes or osteochondral plugs to the lesion area. However, these techniques have the problem of limited cell and tissue sources available for transplantation. Therefore, cartilage engineering and use of mesenchymal stem cells have raised a lot of interest as therapeutic approaches. Various strategies are being tested for their ability to provide tissue constructs that could be used as a replacement for the damaged cartilage. Growth factors, cytokines and mechanical forces are known to direct chondrogenesis and the maintenance of chondrocytic phenotype, although the cellular signaling events involved are often poorly known. Yet, understanding of the signal transduction mechanisms involved in chondrogenesis and cartilage tissue engineering will be very important, especially to learn how to guide stem cells into the desired differentiation path. This review aims to summarize the known signal transduction pathways involved with osteoarthritis, cartilage mechanobiology and differentiation of mesenchymal stem cells to chondrocytes.

  • 138.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Current perspectives on cartilage and chondrocyte mechanobiology.2004In: Biorheology, ISSN 0006-355X, E-ISSN 1878-5034, Vol. 41, no 3-4, p. 593-596, article id 15299289Article, review/survey (Refereed)
    Abstract [en]

    It is well known that physiological forces are essential for the maintenance of normal composition and structure of articular cartilage. Although some of the mechanisms of mechanotransduction are known today, there are certainly many others left unrevealed. In order to understand the complicated systems present in articular cartilage, we have to bring together the data from all fields of cartilage mechanobiology. The 3rd Symposium on Mechanobiology of Cartilage and Chondrocyte was a good effort towards that goal.

  • 139.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Influences of in vivo and in vitro loading on the proteoglycan synthesis of articular cartilage chondrocytes1993Doctoral thesis, monograph (Other academic)
    Abstract [en]

    In this study, the biosynthesis of proteoglycans (PGs) was examined in articular cartilage of canine hip joint after long-distance running experiment and in bovine chondrocyte cultures during in vitro loading with hydrostatic pressure. In addition, new assays were developed for more sensitive quantitation of glycosaminoglycans (GAGs) and PGs.

    Anterior (weight-bearing) and posterior (less weight-bearing) areas of the femoral head from young beagles were labeled after long-term, longdistance running exercise. Total sulpahte incorporation rates were determined and distribution of of the incorporated sulphate in the tissue was localized by quantitative autoradiography. Concentration and extractability of the PGs were determined, and PG structures were studied by gel filtration, agarose gel electrophoresis, and chemical determinations. In the less weight-bearing area, the amount of extractable PGs was decreased, simultaneously with an increased concentration of residual GAGs in the tissue after 4M GuCl extraction. In the weight-bearing area, no marked alterations were noticed. The congruency of the femoral head seems to protect the cartilage from untoward alterations that occur in the femoral head condyles subjected to the same running program.

    The effect of hydrostatic pressure on PG metabolism of chondrocyte cultures was examined during 20 hours' exposure of chondrocytes to 5 and 30 MPa pressures. The continuous 30 MPa pressure reduced total PG synthesis by 37 % as measured by [35S]sulphate incorporation, in contrast to the 5 MPa which had no effect. Continuous 30 MPa hydrostatic pressure also reduced the steady-state mRNA level of aggrecan. The cyclic pressures showed a frequency dependent stimulation (0.5 Hz, + 11 %) or inhibition (0.017 Hz, -17 %). Aggrecans secreted under continuous 30 MPa pressure showed a retarded migration in 0.75 % SDS-agarose gel electrophoresis and also eluted earlier on Sephacryl S-1000 gel filtration, indicative of larger molecular size. The results demonstrate that high hydostatic pressure can influence the synthesis of PGs in chondrocytes both at the transcriptionl and translational/posttranslational levels.

  • 140.
    Lammi, Mikko
    et al.
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Häkkinen, Tomi
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Parkkinen, Jyrki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Hyttinen, Mika
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Jortikka, Matti
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Markku
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Adaptation of canine femoral head articular cartilage to long distance running exercise in young beagles.1993In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 52, no 5, p. 369-377, article id 8323385Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the effects of long term (one year), long distance (up to 40 km/day) running on the metabolism of articular cartilage the biosynthesis of proteoglycans was examined by in vitro labelling of anterior (weight bearing) and posterior (less weight bearing) areas of the femoral head from young beagles.

    METHODS: Total sulphate incorporation rates were determined and distribution of the incorporated sulphate was localised by quantitative autoradiography. Concentration and extractability of the proteoglycans were determined, and proteoglycan structures were investigated by gel filtration chromatography, agarose gel electrophoresis, and chemical determinations.

    RESULTS: In the less weight bearing area the amount of extractable proteoglycans was decreased (p < or = 0.02), simultaneously with an increased concentration of residual glycosaminoglycans in the tissue after 4 M GuCl extraction (p < or = 0.05). In control animals proteoglycan synthesis was most active in the deep zone of the cartilage, whereas exercise increased synthesis in the intermediate zone. There was a tendency to a lower keratan: chondroitin sulphate ratio in the running dogs. No macroscopical or microscopical signs of articular degeneration or injury were visible in any of the animals.

    CONCLUSION: The articular cartilage of the femoral head showed a great capacity to adapt to the increased mechanical loading. The reduced proteoglycan extractability in the less weight bearing area changed it similar to the weight bearing area, suggesting that the low extractability of proteoglycans reflects the long term loading history of articular cartilage. The congruency of the femoral head with acetabulum seems to protect the cartilage from the untoward alterations that occur in the femoral condyles subjected to a similar running programme.

  • 141.
    Lammi, Mikko
    et al.
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Häkkinen, Tomi
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Parkkinen, Jyrki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Hyttinen, Mika
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Jortikka, Matti
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Markku
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Effects of long-term running exercise on canine femoral head articular cartilage.1993In: Agents and actions. Supplements, ISSN 0379-0363, Vol. 39, p. 95-99, article id 8456648Article in journal (Refereed)
    Abstract [en]

    After long-term running program (40 km/day) anterior and posterior tissue samples from canine femoral head were labeled ex vivo in the presence of 35S-SO4. Sulfate incorporation rates did not differ between runner and control groups. The statistically significant changes in runners included a decreased uronic acid concentration (p < or = 0.02) and proportion of extractable proteoglycans (p < or = 0.05) as well as increased concentration of tissue uronic acid after 4 M GuCl extraction (p < or = 0.05) in the posterior area. These results support an idea of strengthened cartilage tissue after this kind of motion and load.

  • 142.
    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 1422-0067, 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.

  • 143.
    Lammi, Pirkko
    et al.
    Department of Clinical Chemistry, Kuopio University Hospital, Kuopio, Finland; Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Hyttinen, Mika
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Panula, Harri
    Department of Surgery, Pietarsaari Hospital, Pietarsaari, Finland.
    Kiviranta, Ilkka
    Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Site-specific immunostaining for type X collagen in noncalcified articular cartilage of canine stifle knee joint.2002In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 31, no 6, p. 690-696, article id 12531563Article in journal (Refereed)
    Abstract [en]

    Type X collagen is a short-chain collagen that is strongly expressed in hypertrophic chondrocytes. In this study, we used an immunohistochemical technique exploiting a prolonged hyaluronidase unmasking of type X collagen epitopes to show that type X collagen is not restricted to calcified cartilage, but is also present in normal canine noncalcified articular cartilage. A 30 degrees valgus angulation procedure of the right tibia was performed in 15 dogs at the age of 3 months, whereas their nonoperated sister dogs served as controls. Samples were collected 7 and 18 months after the surgery and immunostained for type X collagen. The deposition of type X collagen increased during maturation from age 43 weeks to 91 weeks. In the patella, most of the noncalcified cartilage stained for type X collagen, whereas, in the patellar surface of the femur, it was present mainly in the femoral groove close to cartilage surface. In femoral condyles, the staining localized mostly in the superficial cartilage on the lateral and medial sides, but not in the central weight-bearing area. In tibial condyles, type X collagen was often observed close to the cartilage surface in medial parts of the condyles, although staining could also be seen in the deep zone of the cartilage. Staining for type X collagen appeared strongest at sites where the birefringence of polarized light was lowest, suggesting a colocalization of type X collagen with the collagen fibril arcades in the intermediate zone. No significant difference in type X collagen immunostaining was observed in lesion-free articular cartilage between controls and dogs that underwent a 30 degrees valgus osteotomy. In osteoarthritic lesions, however, there was strong immunostaining for both type X collagen and collagenase-induced collagen cleavage products. The presence of type X collagen in the transitional zone of cartilage in the patella, femoropatellar groove, and in tibial cartilage uncovered by menisci suggests that it may involve a modification of collagen fibril arrangement at the site of collagen fibril arcades, perhaps providing additional support to the collagen network.

  • 144.
    Lammi, Pirkko
    et al.
    Department of Clinical Chemistry, Kuopio University Hospital, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Raija
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Espanha, Maria
    Strong hyaluronan expression in the full-thickness rat articular cartilage repair tissue.2001In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 115, no 4, p. 301-308, article id 11405058Article in journal (Refereed)
    Abstract [en]

    Articular cartilage lesions have a poor capacity to regenerate. In full-depth articular cartilage defects, the repair process involves an ingrowth of mesenchymal cells from the bone marrow to the injured area, and these cells attempt to restore the lesion with cartilage-like repair tissue. In this study, we investigated histologically the distribution of hyaluronan in the rat repair tissue in relation to other glycosaminoglycans. Full-depth lesions were drilled to the weight-bearing region of rat medical femoral condyle. The rats were divided into two groups: intermittent active motion (IAM) and running training (RT) groups. In the RT group, programmed exercise was started 1 week after surgery, while the rats in the IAM group could move freely in their cages. The lesions were investigated 4 and 8 weeks after the surgery. Semiquantitative histological grading showed no significant differences in the repair between the groups. In normal articular cartilage, hyaluronan was stained mainly around chondrocytes. During repair, strong hyaluronan staining was observed in loose mesenchymal tissue, while in the repair area undergoing endochondral ossification, hyaluronan was intensively stained mainly around the hypertrophic chondrocytes. Remarkably strong staining for hyaluronan was noticed in areas of apparent mesenchymal progenitor cell invasion, the areas being simultaneously devoid of staining for keratan sulphate. In conclusion, hyaluronan is strongly expressed in the early cartilage repair tissue, and its staining intensity and distribution shows very sensitively abnormal articular cartilage structure.

  • 145.
    Larsson, Johanna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Biological age of growing individuals with patellar dislocation: A study of the growth plate examined with MRI of patients aged 10 – 20 years2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 146.
    Lei, Yang
    et al.
    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, Shaanxi, P.R. China.
    Guanghui, Zhao
    Hong Hui Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
    Xi, Wang
    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, Shaanxi, P.R. China.
    Yingting, Wang
    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, Shaanxi, P.R. China.
    Xialu, Lin
    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, Shaanxi, P.R. China.
    Fangfang, Yu
    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, Shaanxi, P.R. China.
    Goldring, Mary
    Hospital for Special Surgery, Weill Cornell Medical College, New York, USA.
    Xiong, Guo
    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, Shaanxi, P.R. 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, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi'an, Shaanxi, P.R. China.
    Cellular responses to T-2 toxin and/or deoxynivalenol that induce cartilage damage are not specific to chondrocytes2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 1, p. 2231-Article in journal (Refereed)
    Abstract [en]

    The relationship between T-2 toxin and deoxynivalenol (DON) and the risk of Kashin-Beck disease is still controversial since it is poorly known about their selectivity in cartilage damage. We aimed to compare the cytotoxicity of T-2 toxin and DON on cell lines representative of cell types encountered in vivo, including human chondrocytes (C28/I2), human hepatic epithelial cells (L-02) and human tubular epithelial cells (HK-2). In addition, we determined the distribution of T-2 toxin and DON in Sprague-Dawley (SD) rats after a single dose exposure. T-2 toxin or DON decreased proliferation in a time- and concentration-dependent manner and their combination showed a similar antagonistic effect in C28/I2, L-02 and HK-2 cells. Moreover, we observed cell cycle arrest and apoptosis, associated with increased oxidative stress and decline in mitochondrial membrane potential induced by T-2 toxin and/or DON. In vivo study showed that T-2 toxin and DON did not accumulate preferentially in the knee joint compared to liver and kidney after an acute exposure in SD rats. These results suggest that T-2 toxin and/or DON inhibit proliferation and induce apoptosis through a possible mechanism involving reactive oxygen species-mediated mitochondrial pathway that is not specific for chondrocytes in vitro or joint tissues in vivo.

  • 147.
    Lerner, Ulf H.
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Centre for Bone and Arthritis Research at Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Kindstedt, Elin
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    The critical interplay between bone resorbing and bone forming cells2019In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 46, p. 33-51Article in journal (Refereed)
    Abstract [en]

    Aim: In this article, the interplay between bone resorbing and bone forming cells is reviewed.

    Method: This review examines the comprehensive literature on the interaction between bone resorption and bone formation.

    Results: Coupling between bone resorption and bone formation refers to the process within basic multicellular units, in which osteoclastic bone resorption is met by the differentiation of osteoblasts and their bone forming activity. There are many possible signalling molecules that contribute to coupling at the asynchronously working remodelling sites throughout our skeleton. These include growth factors released from the bone matrix during bone resorption, soluble and membrane products of the osteoclasts and their precursors and signals from osteocytes.

    Conclusions: In this review, we describe the potential roles of a number of these factors, whose interactions are essential for a tight control of coupling within individual remodelling units, in order to control skeletal mass. Both pre‐clinical evidence and clinical evidence pinpoint that molecules in the WNT signalling pathway could be promising bone augmentation therapeutic targets. Regarding oral implications, there is support, from preclinical studies in rats, that anti‐sclerostin antibodies can restore alveolar bone mass.

  • 148.
    Lerner, Ulf H
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Centre for Bone and Arthritis Research, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Ohlsson, C
    Centre for Bone and Arthritis Research, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    The WNT system: background and its role in bone2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 6, p. 630-649Article in journal (Refereed)
    Abstract [en]

    WNTs are extracellular proteins that activate different cell surface receptors linked to canonical and noncanonical WNT signalling pathways. The Wnt genes were originally discovered as important for embryonic development of fruit flies and malignant transformation of mouse mammary cancers. More recently, WNTs have been implicated in a wide spectrum of biological phenomena and diseases. During the last decade, several lines of clinical and preclinical evidence have indicated that WNT signalling is critical for trabecular and cortical bone mass, and this pathway is currently an attractive target for drug development. Based on detailed knowledge of the different WNT signalling pathways, it appears that it might be possible to develop drugs that specifically target cortical and trabecular bone. Neutralization of a bone-specific WNT inhibitor is now being evaluated as a promising anabolic treatment for patients with osteoporosis. Here, we provide the historical background to the discoveries of WNTs, describe the different WNT signalling pathways and summarize the current understanding of how these proteins regulate bone mass by affecting bone formation and resorption.

  • 149.
    Leskinen, Jarkko
    et al.
    Deaprtment of Physics, University of Kuopio, Kuopio, Finland.
    Karjalainen, Hannu
    Institute of Biomedicine, Anatomy, University of Kuopio, Kuopio, Finland.
    Olkku, Anu
    Institute of Biomedicine, Medical Biochemistry, University of Kuopio, Kuopio, Finland.
    Hynynen, Kullervo
    Deaprtment of Physics, University of Kuopio, Kuopio, Finland.
    Mahonen, Anitta
    Institute of Biomedicine, Medical Biochemistry, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Genome-wide microarray analysis of MG-63 osteoblastic cells exposed to ultrasound.2008In: Biorheology, ISSN 0006-355X, E-ISSN 1878-5034, Vol. 45, no 3-4, p. 345-354, article id 18836235Article in journal (Refereed)
    Abstract [en]

    It is well documented that low intensity pulsed ultrasound can be clinically used to accelerate bone fracture healing. Additionally, in vitro studies have shown that ultrasound can, for instance, increase mineralization, collagen production and alkaline phosphatase activity in osteoblasts. Despite the extensive research on the subject, the exact mechanism of ultrasound effect on bone cell gene regulation has not yet been deduced. In this study, we made an effort to reveal the features of genome-wide transcriptional response of osteoblast-type cells to ultrasound. MG-63 osteoblastic cell transcriptome was analyzed with whole genome microarray either 6 or 24 h after 30 min long exposure to 1.035 MHz pulsed ultrasound with three different acoustic pressures. Special attention was paid to the experimental design to minimize thermal effects and unwanted reflections of ultrasound. Microarray analysis suggested that ultrasound affects the genes involved with cellular membranes, and regulation of transcription as well. Several plasma membrane solute carriers were also regulated by ultrasound. It also changed the transcript level of several transcription factors belonging to the zinc finger proteins. However, ultrasound did not clearly promote genes involved with osteoblast differentiation.

  • 150.
    Li, Chunyan
    et al.
    1Faculty of Public Health, Medical College of Xi’an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry of Education, Key Laboratory of Trace elements and Endemic Diseases of Ministry of Health, Xi’an, China; Institute of Health Education of Xi’an, Xi’an, China.
    Wang, Weizhuo
    Department of Orthopedics Surgery, Second Hospital, Xi’an Jiaotong University, Xi’an, China.
    Guo, Xiong
    Faculty of Public Health, Medical College of Xi’an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry of Education, Key Laboratory of Trace elements and Endemic Diseases of Ministry of Health, Xi’an, China.
    Zhang, Feng
    Faculty of Public Health, Medical College of Xi’an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry of Education, Key Laboratory of Trace elements and Endemic Diseases of Ministry of Health, Xi’an, China.
    Ma, Weijuan
    Faculty of Public Health, Medical College of Xi’an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases of Ministry of Education, Key Laboratory of Trace elements and Endemic Diseases of Ministry of Health, Xi’an, China.
    Zhang, Yingang
    Department of Orthopedics Surgery, First Hospital, Xi’an Jiaotong University, Xi’an, China.
    Li, Youfen
    School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, China.
    Bai, Yidong
    Department of Cellular and Structural Biology, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas, USA.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Pathways related to mitochondrial dysfunction in cartilage of endemic osteoarthritis patients in China2012In: Science China Life Sciences, ISSN 1674-7305, Vol. 55, no 12, p. 1057-1063, article id 23233220Article in journal (Refereed)
    Abstract [en]

    n this paper, we present the first evidence of differences in the mitochondria-related gene expression profiles of adult articular cartilage derived from patients with Kashin-Beck disease and normal controls. The expression of 705 mitochondria-related genes was analyzed by mitochondria-related gene expression analysis and ingenuity pathways analysis. Mitochondria-related gene expression analysis identified 9 up-regulated genes in Kashin-Beck disease based on their average expression ratio. Three canonical pathways involved in oxidative phosphorylation, apoptosis signaling and pyruvate metabolism were identified, which indicate the involvement of mitochondrial dysfunction in the pathogenesis of Kashin-Beck disease.

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