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

我们通过启动子分析确定了诱导ADAMTS5的转录因子，ADAMTS5是骨关节炎发展的关键蛋白酶。该基因敲除小鼠的原代软骨细胞内源性Adamts 5表达降低。在离体培养的股骨头软骨从间充质细胞特异性敲除该基因，aggrecanolysis显着低于对照软骨。最后，我们在条件性基因敲除小鼠中建立了实验性小鼠骨关节炎模型，该基因的条件性敲除由于软骨细胞凋亡的上调而导致骨关节炎发展的加速。我们将通过使用与该基因相关的信号抑制剂来研究适度抑制该基因可以抑制骨关节炎的发展。

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.