Biochemical elucidation of mandibular condyle cartilage destruction mechanism

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In order to elucidate the mechanism of cartilage degradation and pathologic progress in osteoarthritis (OA), we carried out series of studies by means of biochemical methods.In 1999, we examined the matrix metabolism and the gene expression of MMP and TIMP in cultured rabbit articular chondrocytes subjected to high magnitude tensile load to clarify the effects of mechanical stress on cartilage degradation. In this study, we clarified that high magnitude tensile load changed cell shape and decreased the production of cartilage matrix molecules such as hyaluronic acid, proteoglycan and type II collagen. In addition, we demonstrated that high magnitude tensile load increased expression of MMP-1, -3, -9 and IL-1β, TNF-α, which were involved in cartilage matrix loss.In conclusion, we revealed in this study that high magnitude tensile load caused the degradation of cartilage directly by reducing the production of matrix molecules and enhancing the expression of catabolic factors.In 2000, we investigated the expression patterns of hyaluronic acid synthetases (HASs), which regulate the molecular weight of hyaluronic acid, and clarified the mechanism of accumulation of low molecular hyaluronic acid in synovial fluid of patients with OA.In this study, we demonstrated that HAS2, which synthesizes the high molecular weight hyaluronic acid, was predominantly expressed in normal synovial membrane and cartilage, whereas HAS3, which synthesizes the low molecular weight hyaluronic acid, was induced highly by proinflammatory cytokaines such as IL-1β and TNF-α.These results suggest that the low molecular weight hyaluronic acid is produced during synthesis by HAS3 induced by cytokines under inflammatory conditions and this low molecular weight HA may cause the reduction of the visco-elasity of synovial fluid, and enhance the inflammatory response.