Comprehensive analysis of the inducer that degrades the extracellular matrix of articular cartilage

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We identified transcription factor that induce ADAMTS5, a crucial proteinase for osteoarthritis development by promotor analysis. The endogenous Adamts5 expression in primary chondrocyte derived from knockout mouse of this gene was decreased. In the ex vivo culture of femoral head cartilage from mesenchymal cell-specific knockout of this gene, aggrecanolysis was significantly lower than that in the control cartilage. Finally, we performed the experimental mouse osteoarthritis model in conditional knockout mouse, the conditional knockout of this gene resulted in the acceleration of osteoarthritis development because of the up-regulation of chondrocyte apoptosis. We will investigate moderate suppression of this gene could suppress the osteoarthritis development by using inhibitor of signals related to this gene.