[Show abstract][Hide abstract] ABSTRACT: Temporomandibular joint (TMJ) osteoarthritis is typically a slowly progressive asymmetric disease. Little is known regarding the natural destruction of TMJ articular tissues. The aim of the present study was to investigate morphological changes in the TMJ of STR/ort mice, known to be the model for spontaneous osteoarthritis in the knee joint, and to evaluate STR/ort mice as a suitable animal model for TMJ osteoarthritis. TMJs from 32 STR/ort mice euthanized at 30, 40, 50 or 60 weeks of age, and from 6 CBA mice euthanized at 30, 40 or 60 weeks of age were examined. Toluidine blue and tartrate-resistant acid phosphatase staining were used to assess histological changes in the articular cartilage. Morphological changes in the articular cartilage of the TMJ were evaluated using microcomputed tomography. At the age of 40-50 weeks, 17 (68%) of the 25 STR/ort mice had loss of articular cartilage on histology, with cavitation and erosion of the exposed bone and gradual changes in condylar shape. Furthermore, osteoarthritic morphological changes, and structural alterations were observed by microcomputed tomography. The STR/ort mouse strain appears to develop spontaneous osteoarthritis-like lesions in the TMJ with age, and would be a useful model to study the pathogenesis of TMJ osteoarthritis.
[Show abstract][Hide abstract] ABSTRACT: Our aim was to explore important inflammatory mediators for synovial chondromatosis in the temporomandibular joints (TMJs) by analysing synovial fluid. Samples were collected from 10 patients with unilateral synovial chondromatosis of the TMJ. Control samples were obtained from 11 subjects with no symptoms in the TMJ. Concentrations of aggrecan, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8 (CXCL8), IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF)-A were measured in the samples of synovial fluid, and the results in the two groups compared. The tissues from the affected TMJ were examined histologically and immunohistochemically. Of the proteins evaluated, the concentrations of aggrecan, IL-6, and VEGF-A were significantly higher in the group with synovial chondromatosis. The immunohistochemical analysis showed that the synovial cells around the osteocartilaginous nodules were vigorously expressing VEGF-A. IL-6 and VEGF-A are thought to have important roles in the pathology of synovial chondromatosis of the TMJ.
British Journal of Oral and Maxillofacial Surgery 04/2012; 51(2). DOI:10.1016/j.bjoms.2012.03.004 · 1.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: When cultured in monolayers, articular chondrocytes undergo an obvious phenotypic change. Although the involvement of integrins has been suggested, the exact mechanisms of the change have not been determined. This study was undertaken to clarify the mechanisms underlying the loss of chondrocyte phenotype early after plating.
Primary cultured human articular chondrocytes were used for the experiments. Involvement of respective integrins in the phenotypic change was investigated in RNA interference (RNAi) experiments. A signaling pathway involved in the change was identified in experiments using specific inhibitors and adenoviruses encoding mutated genes involved in the pathway. Adenoviruses carrying mutated GTPases were used to determine the involvement of small GTPases in the process.
In monolayer-cultured chondrocytes, suppression of αv or β5 integrin expression by RNAi inhibited morphologic changes in the cells and increased (or prevented a reduction in) the expression of various cartilage matrix genes. Consistent results were obtained in experiments using a blocking antibody and a synthetic inhibitor of αvβ5 integrin. The decrease in cartilage matrix gene expression in chondrocytes after plating was mediated by ERK signaling, which was promoted primarily by αvβ5 integrin. In articular chondrocytes, the affinity of αvβ5 integrin for ligands was regulated by the small GTPase R-Ras. R-Ras was gradually activated in monolayer-cultured chondrocytes after plating, which caused a gradual decline in cartilage matrix gene expression through enhanced αvβ5 integrin activation and the subsequent increase in ERK signaling.
Our findings indicate that αvβ5 integrin may be involved in the change that occurs in monolayer-cultured chondrocytes after plating.
[Show abstract][Hide abstract] ABSTRACT: To investigate the changes of knee menisci in osteoarthritis (OA) in human.
OA and control menisci were obtained from 42 end-stage OA knees with medial involvement and 28 non-arthritic knees of age-matched donors, respectively. The change of menisci in OA was evaluated by histology, and gene expression of major matrix components and anabolic factors was analyzed in the anterior horn segments by quantitative PCR (qPCR). In those regions of menisci, the rate of collagen neo-synthesis was evaluated by [(3)H]proline incorporation, and the change of matrix was investigated by ultrastructural observation and biomechanical measurement.
In OA menisci, the change in histology was rather moderate in the anterior horn segments. However, despite the modest change in histology, the expression of type I, II, III procollagens was dramatically increased in those regions. The expression of insulin-like growth factor 1 (IGF-1) was markedly enhanced in OA menisci, which was considered to be responsible, at least partly, for the increase in procollagen gene expression. Interestingly, in spite of marked increase in procollagen gene expression, incorporation of [(3)H]proline increased only modestly in OA menisci, and impaired collagen synthesis was suggested. This finding was consistent with the results of ultrastructural observation and biomechanical measurement, which indicated that the change of meniscal matrix was modest in the macroscopically preserved areas of OA menisci.
Although the expression of major matrix components was markedly enhanced, matrix synthesis was enhanced only modestly, and the changes of matrix in human OA menisci were rather modest in the non-degenerated areas.
Osteoarthritis and Cartilage 09/2010; 18(9):1133-43. DOI:10.1016/j.joca.2010.05.017 · 4.17 Impact Factor