KIAA1199在骨关节炎软骨基质降解中的作用及机制研究

项目名称： KIAA1199在骨关节炎软骨基质降解中的作用及机制研究

项目编号： No.81501906

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： 丁钱海

作者单位： 浙江大学

项目金额： 18万元

中文摘要： 骨关节炎（Osteoarthritis,OA）以软骨基质破坏为主要特点，是骨科的常见病和多发病，其发病机制仍不明确。探索关键的致病因子和药物作用靶点，是OA治疗研究的重要方向。近期研究表明：KIAA1199在侵袭性肿瘤组织中表达升高，且KIAA1199可促进皮肤成纤维细胞中透明质酸的分解。但是，KIAA1199在OA中的研究尚无报道。我们前期研究发现：OA患者关节软骨高表达KIAA1199，其血清KIAA1199水平较非OA患者显著上调；同时，KIAA1199调控软骨细胞内基质代谢及影响降解酶系统表达，从而参与OA软骨破坏的病理过程。本课题以人软骨细胞、动物模型及临床标本为研究对象，应用基因沉默与过表达、细胞信号通路抑制/激活、动物实验等方法深入研究KIAA1199在OA病程中对软骨基质代谢调控的分子机理和信号传导机制。本课题将进一步揭示OA的发病机制，为OA的治疗研究提供新的思路。

中文关键词： KIAA1199；骨关节炎；软骨降解；Wnt/β-catenin

英文摘要： Osteoarthritis (OA) is a common and frequently-occurring orthopaedic disease, characterized by cartilage degradation and its causes remain unclear. To explore key relative factors and drug targets is an important research direction of OA treatment. Recent studies reveal that the expression of KIAA1199 is increased in invasive tumor tissues and KIAA1199 may promote the catabolism of hyaluronic acid in skin fibroblasts. However, little is known about the role of KIAA1199 in OA. Our previous study found that: the levels of KIAA1199 were significantly higher in OA cartilage and serum than non-OA donors; KIAA1199 can regulate intra-cellular matrix metabolism, affecting the degrading enzyme expression and mediate the pathological process involved in cartilage destruction. In this study, we will take human chondrocytes, animal OA model and clinical specimens as objects to further investigate the role of KIAA1199 in the process of cartilage degradation and abnormal signal transduction. Gene silence and over-expression, signal pathway inhibitor and agonist as well as animal experimentation are used in this present study. Our study will further reveal the pathogenesis of OA, and provide new ideas for the treatment of OA.

英文关键词： KIAA1199;osteoarthritis;cartilage degradation ;Wnt/β-catenin