SOST在骨性关节炎中的作用机制和应用研究

项目名称： SOST在骨性关节炎中的作用机制和应用研究

项目编号： No.81472116

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： 滕华建

作者单位： 南京大学

项目金额： 90万元

中文摘要： 骨性关节炎是一种最为常见的骨关节疾病，该病的主要病理改变涉及软骨病损和异常骨形成，迄今尚无有效的药物学治疗措施。研究表明，SOST作为Wnt信号通路的抑制因子在骨细胞中表达，在骨形成调节中起关键作用。尽管软骨细胞表达SOST，但其潜在的作用仍然不确定。本项目拟在前期工作基础上，采用定量PCR、免疫杂交、免疫共沉淀、免疫组织化学、染色体免疫共沉淀分析、基因报告分析、基因沉默等技术，并结合SOST基因敲除和高表达小鼠制作的关节炎动物模型，揭示SOST在软骨细胞中表达及调控的分子机制，探讨其在软骨形成和骨性关节炎发生、发展中的作用。通过本项研究，不仅将丰富我们对骨性关节炎发病机制以及软骨形成调节的认识，而且有可能为骨性关节炎的临床防治开辟一条新途径。

中文关键词： 骨性关节炎；软骨修复；软骨细胞分化；SOST

英文摘要： Osteoarthritis (OA) is by far the most common type of joint disease, which is characterized by abnormal articular chondrocyte differentiation, articular cartilage degradation and osteophyte formation. There is no disease-modifying drug for OA treatment to date. It has been shown that SOST, acting as an inhibitor of Wnt signaling pathway, plays a critical important role in the regulation of bone formation. While SOST is expressed in chondrocyte, the potential roles and mechanisms of SOST in OA and cartilage formation still remain to be uncovered. Through application of molecular techniques (such as real-time PCR, Western blotting, immunoprecipitation, luciferase report assay, Chip assay, siRNA etc al) and preparation of OA animal models in SOST-KO and TG mouse, we will characterize the expression patterns of SOST in chondrocytes and assess the roles of SOST in the development of OA and chondrogenesis. Furthermore, the molecular mechanism of tissue-specific expression of SOST will also be investigated. Therefore, this study may provide a new theoretical basis of understanding physiological and pathological roles of SOST in OA and even in cartilage development, and potential discoveries may make them a promising target for therapeutic interventions in OA.

英文关键词： osteoarthritis;cartilage healing;chondrocyte differentiation;SOST