Cadherin 11在骨关节炎滑膜炎及关节软骨破坏中的作用机制

项目名称： Cadherin 11在骨关节炎滑膜炎及关节软骨破坏中的作用机制

项目编号： No.81472123

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： 孙铁铮

作者单位： 北京大学

项目金额： 72万元

中文摘要： 骨关节炎（osteoarthritis, OA）是累及整个关节器官包括软骨、滑膜、软骨下骨等各种组织的病变；滑膜炎是造成OA疼痛、炎症和软骨破坏的主要原因，与OA病情进展密切相关。炎症可能成为OA病情控制新的靶点及病情评估的有效标志。Cadherin 11是滑膜衬里层形成的关键粘附分子，在类风湿滑膜炎中表达增多并参与软骨侵蚀进程，Cadherin 11敲除小鼠关节软骨破坏受到明显抑制。我们前期研究发现，OA滑膜组织中Cadherin 11增高，并与滑膜炎性程度密切相关。本课题拟分析OA滑膜组织Cadherin 11表达上调的分子机制，采用shRNA慢病毒转染技术，观察Cadherin 11在OA滑膜细胞侵袭和迁移，促进炎性因子的分泌和软骨破坏中的作用，在OA小鼠模型中验证抗Cadherin 11治疗对滑膜炎和软骨破坏的影响，为Cadherin 11作为骨关节炎新的分子治疗靶点提供实验证据。

中文关键词： 骨关节炎；cadherin；11；滑膜细胞；软骨退变

英文摘要： Primary osteoarthritis (OA) was a complex, multifactorial inflammatory disease of the whole joint. The synovium, bone and cartilage were each involved in pathological processes that lead to progressive joint degeneration. The presence of synovitis was associated with more severe pain, joint dysfunction and increased risk of radiographic evidence of disease progression. Cadherin-11, a newly specific marker expressed on fibroblast-like synoviocytes(FLS), was not only indispensable for the development of the normal synovium lining layer, but also was the crucial molecule in driving synovial inflammation and cartilage erosions in rheumatoid arthritis. Cadherin-11 deficient mice showed resistant to inflammatory arthritis and strongly protected against cartilage destruction. However, few studies about the correlation between OA synovitis and cadherin-11 expression have been published. Our prior studies showed that expression of cadherin-11 increased with the synovitis severity in osteoarthritis. In this study, we will investigate the molecular mechanism of cadherin-11 over expression in osteoarthritis; also with lentivirus transfection containing cadherin 11 shRNA, explore the role of cadherin 11 in migration or invasion capacity, production of MMPs and inflammatory mediators in OA FLS, and observe the effect of anti-cadherin 11 in collagenase induced osteoarthritis in C57 BL/6 mice,which might provide a potent candidate molecule for therapeutic target of OA.

英文关键词： osteoarthritis;cadherin 11;synovitis;cartilage destruction