R-spondin 3对类风湿关节炎成纤维样滑膜细胞迁移和侵袭的调控及机制研究

成纤维样滑膜细胞（FLS）的异常迁移和侵袭在类风湿关节炎(RA)关节破坏和疾病进展中起关键作用。我们前期实验通过基因芯片筛选以及RT-qPCR验证，发现R-spondin 3在RA FLS和RA滑膜组织中表达显著高于正常人，干扰R-spondin 3可显著抑制RA FLS体外迁移和侵袭能力，并抑制与RA FLS迁移侵袭密切相关的β-catenin。因此，本课题拟在我们前期工作基础上，进一步证实R-spondin 3对RA滑膜侵袭的重要调控作用，并利用Co-IP、TOP/FOP Flash等方法阐明R-spondin 3如何通过Wnt/β-catenin通路调节RA滑膜迁移、侵袭，旨在进一步揭示RA滑膜侵袭和关节破坏发生的分子机制，为RA治疗提供新思路。

Abnormal migration and invasion of fibroblast like synoviocytes (FLS) play a key role in controlling the process of joint destruction and synovium inflammation in rheumatoid arthritis (RA). We found that R-spondin 3 is significantly upregulated in RA FLS and RA synovium tissue compared with Healthy controls(HC). It is mainly located in the cytoplasm. Using siRNA of R-spondin 3 could significantly inhibit migration and invasion of RA FLS in vitro, as well as Wnt/β-catenin signalling pathway which plays a key role in RA pathology. Based on these results, we assumed that R-spondin 3 interferes migration and invasion of RA FLS through Wnt/β-catenin. Methods including in vitro/vivo migration and invasion experiments of RA FLS, Co-IP, TOP/FOP Flash assay will be used to clarify the underlying mechanism how R-spondin 3 effect on the abnormal functions of RA FLS, providing the scientific basis for the establishment of a novel therapeutic target for RA.