BMMSCs来源外泌体对类风湿关节炎滑膜细胞的作用

Effect of BMMSCs derived exosomes on rheumatoid arthritis synoviocytes

[目的]探索骨髓间充质干细胞来源的外泌体对类风湿关节炎滑膜成纤维细胞(Rheumatoid arthritis synovial fibroblasts,RA-FLS)的作用以及相关作用机制,以期为类风湿关节炎治疗提供新思路。[方法]将类风湿关节炎滑膜成纤维细胞分为4组,分别用0、1、3、5μmol/L的人骨髓间充质干细胞来源的外泌体进行处理。MTT实验和流式细胞术评估细胞损伤情况;Transwell实验分析细胞迁移能力;ELISA试剂检测炎症因子的含量;蛋白免疫印迹实验分析p38蛋白激活情况。[结果]骨髓间充质干细胞来源的外泌体能够降低RA-FLS迁移能力(198.56±10.89 vs 31.27±1.66),并能促进RA-FLS发生凋亡(6.26%±0.09%vs 23.56%±1.21%)。人骨髓间充质干细胞来源的外泌体还能减少RA-FLS分泌的炎症细胞因子。人骨髓间充质干细胞来源的外泌体能够抑制p38蛋白磷酸化(0.89±0.02 vs 0.11±0.01)。[结论]人骨髓间充质干细胞来源的外泌体能够抑制RA-FLS生长和转移,抑制RA-FLS分泌炎症因子,这些作用与抑制p38 MAPK激活有关。

[Objective]To explored the effects of exosomes derived from bone marrow mesenchymal stem cells on rheumatoid arthritis synovial fibroblasts(RA-FLS)and the related mechanisms,in order to provide a new way of thinking for the treatment of rheumatoid arthritis.[Method]RA-FLS were divided into four groups and treated with 0,1,3,and 5μmol/L of human bone marrow mesenchymal stem cell-derived exosomes.MTT assay and flow cytometry were used to evaluate cell damage.Transwell assay was used to analyze cell migration ability.ELISA was used to detect the content of inflammatory factors.The activation of p38 was analyzed by Western Blot.[Result]Exosomes derived from bone marrow mesenchymal stem cells could reduce the migration ability of RA-FLS(198.56±10.89 vs 31.27±1.66)and promote the apoptosis of RA-FLS(6.26%±0.09%vs 23.56%±1.21%).Human bone marrow mesenchymal stem cell-derived exosomes also reduced the secretion of inflammatory cytokines by RA-FLS.Human bone marrow mesenchymal stem cells-derived exosomes inhibited the phosphorylation of p38 protein(0.89±0.02 vs 0.11±0.01).[Conclusion]Human bone marrow mesenchymal stem cell-derived exosomes can inhibit the growth and metastasis of RA-FLS and inhibit the secretion of inflammatory factors by RA-FLS.These effects are related to the inhibition of p38 MAPK activation.