FGF9在关节软骨稳态维持及OA中的作用与机制研究

项目名称： FGF9在关节软骨稳态维持及OA中的作用与机制研究

项目编号： No.81472074

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杜晓兰

作者单位： 中国人民解放军第三军医大学

项目金额： 72万元

中文摘要： 骨性关节炎（OA）是中老年人常见多发病，多累及负重关节，导致功能障碍，目前没有有效安全的防治药物，严重影响人类健康。关节软骨细胞外基质代谢异常与软骨细胞异常肥大分化是OA的两个重要致病因素。FGF9是调控软骨内成骨及关节发育的重要调控分子，前期我们发现FGF9关节内注射可以缓解小鼠OA模型的关节软骨损伤退变，但具体机制不清楚，有报道提示FGF9与Wnt/β-Catenin在多个组织包括软骨中存在串话。为进一步在整体动物水平明确FGF9在关节软骨稳态维持及OA发生中的作用及机制，我们将利用在软骨细胞可诱导敲除或增强FGF9以及Wnt/β-Catenin的小鼠模型与TOP-gal报道小鼠，结合小鼠OA模型，研究FGF9在小鼠关节软骨稳态维持及OA发生中的作用，并明确Wnt/β-Catenin等信号分子在其中的作用。本研究将揭示FGF9在关节软骨稳态维持中的作用与机制，为研发基于FGF9的防治。

中文关键词： 成纤维细胞生长因子9；骨性关节炎；关节软骨稳态；关节软骨修复

英文摘要： Osteoarthritis (OA) is a frequently-occurred disease in the elderly, which mainly affects the weight-bearing joints, causing dysfunction. There is no effective drug for OA. Abnormally increased degradation of extracellular matrix and premature differentiation of chondrocytes are two important pathogenic factors in OA. FGF9 plays an important role in regulating the endochondral ossification and joint development. We recently found that intra-articular injection of FGF9 can relieve the articular cartilage degeneration of OA mice, but the underlying mechanism is still unclear, and studies have indicated that there is crosstalk between FGF9 and Wnt/β-Catenin in multiple tissues including the cartilage. In order to identify the role of FGF9 in the maintainence of articular cartilage homeostasis in vivo, we will employ inducible chondrocyte-specific knockout or overexpression of FGF9 or β-Catenin mouse models and TOP-gal reporter mice,by making OA model in these mouse strains, to dissect the roles of FGF9 in the maintainence of articular cartilage homeostasis and the role of β-Catenin in it. This study will clarify the role and mechanism of FGF9 in the regulating the homeostasis of articular cartilage, providing the experimental data for the development of FGF9-based drugs against OA.

英文关键词： FGF9;osteoarthritis;homeostasis of articular cartilage;repair of articular cartilage