从Wnt通路靶向调节OPN探讨骨关节炎发病的分子机制

项目名称： 从Wnt通路靶向调节OPN探讨骨关节炎发病的分子机制

项目编号： No.81201420

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 高曙光

作者单位： 中南大学

项目金额： 23万元

中文摘要： 骨关节炎(OA)是一种累及软骨、滑膜和软骨下骨等结构的疾病。Wnt/β-catenin通路与软骨细胞功能行为等密切相关，我们曾证实Wnt抑制因子1、β-catenin与软骨退变程度相关。OPN是一种糖蛋白，我们也证实其在OA患者软骨和滑膜中高表达。先前研究提示，Wnt通路调控OPN预测结肠癌的生存率。但Wnt通路和OPN在OA中的具体调控机制及其是否是OA有效治疗靶点尚未明确。我们推测OA中Wnt通路对OPN有一定调控作用，且在其作用途径中给予siRNA干扰可能延缓甚至阻止OA的进展。为证实这一假说，我们采用EMSA、siRNA等分子生物学技术，观察关节内组织和细胞中Wnt通路成员和OPN的表达，探讨Wnt通路靶向调控OPN介导关节OA改变的作用和机制，明确靶基因siRNA对OA的效应。本课题将从新的视觉阐明OA的发病和发展机制，为探寻OA新的治疗方法提供新的靶分子。

中文关键词： Wnt 通路；骨桥蛋白；骨关节炎；siRNA；

英文摘要： The current concept holds that osteoarthritis (OA) involves not just the articular cartilage but the entire joint organ, including the synovium and subchondral bone. Wnt/β-catenin signaling is associated with chondrocyte function and behavior. Our previous study revealed WIF-1 and β-catenin correlated with the degree of cartilage degeneration. Osteopontin (OPN) is a phosphorylated acidic glycoprotein. We also had showed OA patients had high OPN expression in synovium and articular cartilage. Moreover, the previous study indicated expression of osteopontin, a target gene of de-regulated Wnt signaling, predicted survival in colon cancer. However, the molecular mechanisms that regulate the expression of OPN are incompletely understood by Wnt signaling in OA and it is not clear if they are very good target for OA therapy. We hypothesized that OPN expression can be regulated by the Wnt pathway in OA and small interfering RNA (siRNA)-mediated inhibition of post-transcriptional events can delay or prevent the progression of OA. To prove this hypothesis, we examine the expression of Wnt pathway components and OPN in joint tissues, chondrocyte and synovial cell from OA patients firstly. Secondly, we elucidate the effect and mechanism of Wnt pathway regulating OPN and inducing osteoarthritis-like changes of joint. Finally

英文关键词： Wnt pathway；OPN；OA；siRNA；