前期工作表明， RA活动期患者血液和关节液中血小板微颗粒（PMP）增高。预实验显示，PMP可促进RA-FLS迁移和侵袭及与Collagen I的粘附，调控RA-FLS中张力纤维装配、丝状和片状伪足的形成，上调RA-FLS中p-FAK（Y397）和MMPs，提示PMP可能通过FAK介导的信号通路调控RA-FLS 的粘附、迁移和侵袭过程。本课题将①明确PMP是否影响RA-FLS与细胞外基质（ECM）（Collagen I、Fibronectin和Matrigel等）的粘附、迁移和侵袭；②明确PMP对RA-FLS的粘附、迁移和侵袭过程是否通过NF-κB介导的信号通路调控MMPs的表达及活性和Rho GTP酶（RhoA、Rac1 和Cdc42等）的表达及活性而实现的；③明确Gen是否影响PMP诱导的RA-FLS与ECM粘附、迁移和侵袭过程。本研究将有助于揭示RA患者体内活化血小板产生的PMP在RA发病中的作用及机制，为继续研究相关信号通路在PMP诱导和Gen抑制RA-FLS与ECM粘附、迁移和侵袭中的作用及在关节软骨侵蚀和骨破坏中的作用及机制的研究打下基础，也可能为RA的治疗提供新靶点。

We have previously found that PMP concentration was increased in the blood and synovial fluids of the patients with RA in the active stage,and PMP could promote the fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) (RA-FLS) adhesion onto the extracellular matrix (ECM), migration and invasion, regulate the stress fibers reorganization and the formation of filopodia and lamellipodia, up-regulate the expression of p-FAK(Y397) and matrix metalloproteinases (MMPs) in RA-FLS after treatment with PMP, suggesting that PMP regulates RA-FLS adhesion, migration and invasion presumablly through FAK-mediated signal pathway.In this item, we will firstly examine whether PMP led to the erosion and destruction of articular cartilage through regulating RA-FLS adhesion onto ECM, migration and invasion at the cellular level and in vivo model,and then we will further clarify whether the PMP induced activation was mediated by FAK to regulate the PI3K or MARK signal pathway to modulate the expression and activity of MMPs, and the expression and distribution of epithelial-mesenchymal transformation (EMT) markers, and the Rho GTPases expression and activity in RA-FLS after treatment with PMP.Finally, we will verify whether Gen decreased the erosion and destruction of articular cartilage in in vivo models by regulating FAK-mediated signaling pathways to affect RA-FLS adhesion onto ECM, migration and invasion induced by PMP. This study will be helpful to improve our understanding the complex pathological process of RA, and provide a new target for the treatment of RA.