脂联素(adiponectin，AD)是血浆中含量最多的脂肪因子，本课题组多年来的工作基础及文献均证实类风湿关节炎患者炎性关节中AD高表达并参与了RA骨侵蚀病理过程，迄今为止作用机制尚不明确。通过基因芯片分析破骨细胞分化过程中基因表达谱变化，申请人原创性发现AD能上调骨桥蛋白（Osteopontin，OPN）表达，而OPN在RA中起招募破骨细胞附着于骨面的角色。因此，我们提出假说：在RA中AD能通过促进关节滑膜组织表达OPN，招募破骨细胞沉积于骨面，启动骨侵蚀程序。本研究通过构建胶原诱导关节炎小鼠模型、滑膜成纤维细胞与破骨细胞共培养模型，采用Real-time PCR、Western-blot、腺病毒载体转染、RNA干扰以及小动物荧光活体成像等技术，系统研究AD对OPN的表达和介导招募破骨细胞的机理，验证上述假说，为治疗RA骨侵蚀寻找新的靶标提供理论与实验依据。

Adiponectin (AD) is the most abundant plasma adipokine. Working basis of our group and literatures showed that the high expression of AD in the inflammatory joint of rheumatoid arthritis (RA) patients, which participates in the pathologic process of RA bone erosion. However, the mechanism is still unclear. By gene chip analysis of the change in gene expression during osteoclast differentiation, we found that AD up-regulated osteopontin (OPN). OPN is an important anchored protein in the osteoclast deposition of RA. We propose the hyposis: AD can recruit the deposition of osteoclasts on the bone surface by promoting synovial osteopontin expression in the RA, and start the process of bone erosion. Therefore, in the present study we will construct CIA (collagen induced arthritis，CIA) mouse model and co-culture synovial fibroblasts and osteoclasts. Using the means of real time PCR, Western blot, adenovirus vector transfection and RNA interference to study the mechanisms of AD-mediated regulation on OPN and bone destruction, verify the above hyposis. These will provide theoretical and experimental evidences for the further research on intervention measures of the relief of bone destruction in RA.