骨关节炎（OA）发病机制十分复杂，已经成为世界性的健康难题，目前尚未出现针对疾病发展的有效治疗药物。我们最近研究发现脱氢表雄酮（DHEA）可通过调控软骨细胞外基质（ECM）“合成--分解”代谢的平衡而有效延缓OA发展，提示DHEA具有抗OA的潜在保护作用。预实验发现，在OA的细胞模型和动物模型中“软骨ECM硬化依赖的Rho/ROCK/MLC信号通路”呈现高活性状态。我们推测软骨ECM硬化依赖的Rho/ROCK/MLC信号途径可能在DHEA抗OA的作用中起到重要作用，DHEA可能通过干预该途径对抗OA。为验证该假说，本课题拟以基因修饰小鼠、兔软骨细胞及组织标本、临床OA标本为研究对象，利用基因沉默、信号通路阻断剂、免疫印迹、激光共聚焦显微镜等技术，多层面研究DHEA作用于“软骨ECM硬化依赖的Rho/ROCK/MLC信号通路”，影响OA疾病发展的具体分子药理机制，为OA的防治提供新干预靶点。

Osteoarthritis pathogenesis is complex which poses a challenging issue for the health globally. However, there are no drugs efficacious for retarding disease progress. Our most recent research demonstrated that DHEA positively modulated the balance between anabolic and catabolic metabolism, consequently inhibited OA development. Our preliminary unpublished data show that matrix stiffness mediated Rho/ROCK/MLC signalling pathway is activated in osteoarthritic chondrocytes and OA animal models. We hypothesize that the matrix stiffness mediated Rho/ROCK/MLC signals might have a crucial role in the molecular mechanism of DHEA’s anti-OA potential. To verify this hypothesis, cartilage tissues from rabbits or conditional knockout mice and samples from OA patients are collected, and multiple techniques including gene silencing, signalling pathway inhibition, western blot and laser confocal microscope are applied. We aim to elucidate the exact molecular mechanism of DHEA action against OA, thus provide novel interfering target for OA therapy.