高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究

项目名称： 高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究

项目编号： No.81501928

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： 王林龙

作者单位： 武汉大学

项目金额： 18万元

中文摘要： 骨关节炎（OA）传统上被认为是关节软骨退行性疾病。近年来，大量证据提示代谢性疾病可能参与OA发生发展。流行病学调查及临床研究发现，糖尿病或高血糖与OA存在相关性。但糖尿病是否可致OA易感，及其可能机制尚未明确。晚期糖基化终产物（AGEs）是糖尿病并发症重要原因，可能介入糖尿病OA发生。我们前期研究发现，糖尿病大鼠关节软骨磨损加重，伴随滑膜炎性改变。已知滑膜炎是OA发病的关键因素。本项目拟通过整体动物和细胞实验，证实糖尿病OA易感现象，阐明高血糖通过AGEs-晚期糖基化终产物受体（RAGE）-蛋白激酶C（PKC）轴激活滑膜炎症通路而致OA易感的潜在机制，并在整体动物水平验证滑膜AGE-RAGE-PKC信号通路在糖尿病OA中的重要作用，探讨其可能的干预措施，为深化糖尿病OA内涵、早期预防和治疗OA提供理论和实验依据。

中文关键词： 骨关节炎；糖尿病；滑膜细胞；RAGE信号通路

英文摘要： Osteoarthritis (OA) is traditionally considered to be articular cartilage degenerative diseases. In recent years, a lot of evidences have suggested that metabolic diseases may be involved in the development of OA. Epidemiological and clinical studies have suggested that diabetes may be an independent risk factor for OA disease. The mechanism of diabetes OA has not been clarified because of lacking relevant research. Advanced glycation end products (AGEs) are important cause of diabetes complications and may be involved in diabetic OA. Our previous experiment results showed that, diabetic rats are susceptible to OA, along with synovitis. It is known that activation of synoviocyte could produce inflammation and degradation factor, causing and aggravating articular cartilage damage, so become a key factor in the pathogenesis of OA. The present project intends to confirm the impact of diabetes on OA susceptibility, clarify the role of synovium in diabetic OA, investigate the intrinsic link among hyperglycemia, AGEs- receptor for advanced glycation end products (RAGE)- protein kinase C (PKC) axis, synovitis and degradation change, pathological cartilage damage and OA susceptibility though cell and animal experiments. And we also intend to validate the important role of synovial AGE-RAGE-PKC signaling pathway in diabetes OA at the whole animal level, to explore the possibility of intervention. This project aims to provide theoretical and experimental evidences for investigating connotation of diabetic OA, early prevention and treatment of OA.

英文关键词： osteoarthritis;diabetes;synoviocyte;RAGE signaling pathway