类风湿关节炎（RA）是一种以滑膜炎和关节骨质破坏为主要特征的致残性疾病，自身免疫功能紊乱及多种炎性介质的产生是导致RA骨破坏的最主要原因。Wnt信号通路是介导异常免疫反应与骨代谢系统之间相互作用的重要通路，而该通路中的抑制蛋白DKK（Dickkopf）-1是近年来新发现的介导免疫炎症与骨破坏的重要桥梁分子。我们及国外的近期研究发现，DKK-1在RA外周血及滑膜细胞中异常增多，并与反映病情轻重的临床指标密切相关，但目前对其在RA滑膜炎及骨破坏中作用机制的报道很少。本研究将针对DKK-1在RA滑膜炎症对骨破坏中的影响这一发病机制中至关重要的问题，以RA患者滑膜组织和胶原诱导关节炎（CIA）模型为平台，应用小干扰RNA（siRNA）基因敲低方法，分别从体内和体外等多方面探索DKK-1在RA骨破坏中的作用机制及潜在的治疗价值，为寻找新的RA免疫治疗靶点奠定实验基础。

Rheumatoid arthritis (RA) is a chronic progressive disease characterized by synovitis and bone erosion. The dysfunction of autoimmune and a great number of proinflammatory cytokines are the most important factor causing bone erosion in RA. Wnt signaling pathway is an important access which mediated the interactions between bone metabolism and abnormal autoimmune reaction.The inhibition protein DKK-1 in this pathway is a new important bridge molecule, which mediated the immune response and bone erosion. Recent studies of us and the aboard indicated that the level of DKK-1 increased abnormally in PBMC and synovial fibroblasts and closely related to the clinical data which reflect the disease activity. There is rare report about the mechanism of DKK-1 in the synovial proliferation and bone erosion in RA. Our study aims to evaluate the roles of DKK-1 in RA pathogenesis in vivo and in vitro, and finding a new target of immunotherapy in RA based on the CIA model, fibroblast-like synoviocytes (FLSs), and the technique of siRNA.