项目名称： 外泌体MiR-3195在骨性关节炎中的作用研究

项目编号： No.81501369

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陈世菊

作者单位： 厦门大学

项目金额： 18万元

中文摘要： 骨性关节炎（OA）是由关节软骨的进行性变性和破坏引起的慢性关节疾病，具体的发病机制尚未完全明确，SOX9影响软骨的发育及分化。微小RNA（miRNA）参与调控软骨功能的调节，研究发现关节液等循环体液中存在被外泌体（exosome）包裹的稳定miRNA。课题组前期通过miRNA芯片以及RT-PCR研究发现膝OA患者关节积液中miR-3195表达增加，生物信息学研究发现其靶向作用于SOX9。我们推测miR-3195以exosome形式由滑膜细胞产生，通过旁分泌形式进入软骨细胞，通过负调控SOX9，调控软骨细胞功能，从而影响OA的发生发展。课题组将进一步通过体外细胞研究miR-3195在软骨及滑膜细胞的交流以及对软骨细胞作用并在OA动物模型进行验证，进一步增加对OA的发病机制认识，为今后OA治疗提供新的治疗靶点。

中文关键词： 骨性关节炎；微小RNA；外泌体；滑膜细胞；软骨细胞

英文摘要： Osteoarthritis is OA is a chronic, highly prevalent joint disease characterized by degradation of articular cartilage and imbalance between cartilage degradation and repair mechanism. Sex determining region Y-box 9（SOX9）is essential for normal cartilage development and function. Some miRNAs participate in the cartilage homeostasis and their deregulation contributing to developing cartilage diseases like OA. Exosomal miRNA are found in synovial fluid. In our previous experiment we found miR-3195 overexpressed in synovial fluid of OA patients and its predicted target is SOX9.We hypothesize miR-3195 is excreted by synoviocytes in exosome and paracrine act on chondrocyte which negative regulates SOX in chondrocyte.We will use luciferase report technique, RT-PCR, Western blot and miRNA transfection to clarify exsomal miR 3195 as ‘messege communication’ between synoviocyte and chondrocyte and its role in chonddrocyte in cellular experiments, and further testfy its role in OA animal model so as to provide a new therapeutic target for OA.

英文关键词： Osteoarthritis;MicroRNA;Exosome;Synoviocyte;Chondrocyte