miR-98在骨关节炎软骨细胞凋亡中的作用及其机制的研究

Osteoarthritis (OA) is the most common chronic progressive osteoarticular disease. MicroRNAs, one of the small molecular RNA family, which can play an important role in the post-transcriptional gene regulation by inhibiting target gene and regulate several physiological and pathophysiological processes.In our prophase research, we have found that chondrocyte apoptosis play the key role in the pathogenesis of osteoarthritis and miR-98 was significantly increased in osteoarthritis.Research shows that miR-98 can regulate Fas and Fas-mediated apoptosis which play a part in chondrocyte apoptosis. This suggested miR-98 may play a role in regulation of chondrocyte apoptosis.This study is planned to build high expression/loss of expression of miR-98 in chondrocyte in vitro and in vivo models of osteoarthritis. Observe the effect of changing the expression of miR-98 on chondrocyte apoptosis and apoptosis related proteins to explore the role and mechanism of miR-98 in chondrocyte apoptosis of osteoarthritis. Moreover，observe the effect of changing the expression of miR-98 on the overall level of osteoarthritis. This study investigate the role of of miR-98 in chondrocyte apoptosis of osteoarthritis at cell, molecular and whole levels, which has important significance to clarify the role of miR-98 in the pathogenesis of osteoarthritis. And provide new ideas and targets for the treatment of osteoarthritis.

骨关节炎是一种常见的慢性退行性骨关节疾病。近年发现的microRNAs广泛参与调控细胞分化、增殖、凋亡等生理及病理生理过程。我们前期研究表明软骨细胞凋亡在骨关节炎的发病机制中起着关键作用，miR-98在骨关节炎中显著升高，而miR-98可调控Fas介导的细胞凋亡，提示miR-98可能参与软骨细胞凋亡的调控。本项目拟在整体和离体小鼠骨关节炎模型上，构建miR-98高/低表达的软骨细胞和miR-98基因沉默及高表达的小鼠膝骨关节炎模型，观察miR-98表达变化对软骨细胞凋亡及凋亡相关蛋白的影响，探寻miR-98对骨关节炎软骨细胞凋亡的调控及相关机制；并从整体水平上观察miR-98对骨关节炎的影响探寻。本项目从分子、细胞和整体水平探讨miR-98对骨关节炎软骨细胞凋亡的影响及相关机制，对于阐明miR-98在骨关节炎发病中的作用具有重要意义，并为骨关节炎治疗提供新的思路和靶点。

骨关节炎是一种常见的慢性退行性骨关节疾病。近年发现的microRNAs广泛参与调控细胞分化、增殖、凋亡等生理及病理生理过程。软骨细胞凋亡在骨关节炎的发病机制中起着核心作用。本项目在骨关节炎细胞及动物模型中，研究miR-98表达变化与软骨凋亡的关系，并明确miR-98对软骨细胞凋亡的调控作用，探讨miR-98对软骨细胞凋亡的调控的分子机制及信号转导途径，明确miR-98直接作用的靶蛋白。研究显示：miR-98在骨关节炎模型中起到促进软骨细胞凋亡、抑制软骨细胞增殖的作用。Bcl-2是软骨细胞凋亡的重要调控基因。进一步研究显示miR-98通过负性调控软骨细胞中Bcl-2的表达抑制软骨细胞凋亡，并证实Bcl-2是miR-98直接作用的靶蛋白。本项目从分子、细胞和整体水平探讨miR-98对骨关节炎软骨细胞凋亡的影响及相关机制，对于阐明miR-98在骨关节炎发病中的作用具有重要意义，并为骨关节炎治疗提供新的思路和靶点。