滑膜细胞异常活化、凋亡和侵袭在类风湿关节炎（RA）发病中起关键作用，但其调控机制尚不明确。最新研究发现乳腺癌缺失基因1(DBC1)通过SIRT1和NF-κB信号通路调控炎症反应、细胞凋亡和肿瘤转移。本项目前期研究发现DBC1不仅与免疫调节相关，还在RA滑膜组织和成纤维样滑膜细胞(FLS)高表达，并与滑膜炎症相关，提示DBC1可能参与RA发病过程。本项目拟进一步扩大临床样本，分析RA滑膜组织DBC1表达水平与临床表型的相关性；通过体外干预DBC1表达，探究DBC1对RA-FLS活化、凋亡和侵袭的调控作用及与SIRT1和NF-κB信号通路的关系；在已成功建立的Dbc1基因敲除小鼠模型基础上，观察Dbc1基因敲除对胶原诱导性关节炎小鼠滑膜炎症和关节损害的改善作用；深入研究DBC1对RA滑膜炎和关节破坏的调控作用及机制，为研制RA治疗新靶点提供理论依据。

Abnormal activation, apoptosis and invasion of synoviocytes play a crucial role in the pathogenesis of rheumatoid arthritis (RA), however, the precise mechanism in regulating this cellular process is still unclear. Recent evidences show that deleted in breast cancer 1(DBC1) is involved in the manipulation of inflammatory response, apoptosis and tumor metastasis through SIRT1 and NF-κB signaling. Our previous work demonstrated that DBC1 was related to immune regulation, also highly expressed in RA synovium and fibroblast-like synoviocytes (FLS), positively correlated to synovial inflammation, suggesting that DBC1 may participate in the pathogenesis of RA. We will collect more samples to analyze the association between synovial expression of DBC1 and RA clinical profiles, and try to know whether DBC1 can regulate activation, apoptosis and invasion depending on SIRT1 and NF-κB signaling through Dbc1 gene silencing in RA-FLS in vitro. Meanwhile Dbc1 knockout mice have been constructed. Compared to Dbc1 wild-type mice, the synovitis and joint erosion may be ameliorated in collagen induced arthritis in Dbc1 knockout mice. Our study will clarify the regulation of synovitis and joint erosion in RA by DBC1. Therefore, we would provide the evidence of new target for the treatment of RA.