周期性机械拉伸对类风湿关节炎和骨关节炎成纤维样滑膜细胞BMP-2表达的影响

Effects of cyclic mechanical stretch on BMP-2 expression in RA and OA fibroblast-like synoviocytes

目的研究周期性拉伸对类风湿关节炎(rheumatoid arthritis,RA)和骨关节炎(osteoarthritis,OA)成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)中骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)表达的影响,探讨力学刺激在不同病理过程中对滑膜组织的作用。方法在正常条件和炎症条件下使用Flex cell 4000周期性力学加载系统,分别对正常、RA、OA来源的人膝关节FLS施加连续2 h和6 h的6%、0.5 Hz的拉应力,比较测定BMP-2 mRNA表达的差异性。结果 2 h的机械拉伸对3种FLS中BMP-2 mRNA的水平均无显著性影响6,h的机械拉伸能够显著升高RA FLS中BMP-2 mRNA的水平。炎症因子(IL-1β)作用2 h对正常FLS无显著影响,作用6 h使其中BMP-2 mRNA的水平显著升高;IL-1β作用2 h和6 h均使RA FLS中BMP-2 mRNA的水平显著升高,但只有作用2 h才使OA FLS中BMP-2 mRNA的水平显著升高,作用6 h对OA FLS中BMP-2 mRNA的水平无显著影响;炎症因子和力学刺激共同作用2 h使正常和RA FLS中BMP-2 mRNA的水平显著升高,作用6 h使正常、RA、OAFLS中BMP-2 mRNA水平均显著升高。结论正常、RA、OA FLS中BMP-2 mRNA对于力学刺激和炎症因子的响应不同,结果提示在RA和OA发病机制中,炎症因子的影响可能比力学刺激更强;力学刺激和IL-1β共同作用6 h后对OA FLS中BMP-2 mRNA产生协同效应,提示两者联合作用对OA病情发展具有一定作用。

Objective To explore the role of mechanical stimulation in synovium under different pathological condi-tions through studying the effects of cyclic mechanical stretch on the expression of bone morphogenetic protein-2（BMP-2） in rheumatoid arthritis（RA） and osteoarthritis（OA） fibroblast-like synoviocytes（FLS）.Method 6% and 0.5 Hz stretch generated by Flex cell 4000 tension systems was applied on normal,RA and OA FLS of human knee joint source under normal and inflammatory conditions for 2 h or 6 h,respectively.Results Cyclic mechanical stretch of 6%,0.5 Hz had no significant effects on the expression of BMP-2 in normal,RA and OA FLS at 2 h,while in RA FLS it increased significantly at 6 h.Inflammatory cytokines（IL-1β） didnt’ influence normal FLS at 2 h,but made BMP-2 mRNA significantly increased at 6 h.IL-1β increased BMP-2 mRNA of RA FLS significantly both at 2 h and 6 h.IL-1β increased BMP-2 mRNA of OA FLS significantly only at 2 h,but had no significant effect at 6 h.The co-effect of IL-1β and cyclic mechanical stretch induced the ascension of BMP-2 expression significantly in normal and RA FLS at 2 h,and in normal,RA and OA FLS at 6 h.Conclusions Response of BMP-2 mRNA to mechanic stimulation and IL-1β in normal,RA and OA FLS were different.Inflammation may play a more important role than mechanical stimulation in the pathogenesis of RA and OA.Synergetic effect in inflammation and mechanical stimulation were found in OA FLS at 6 h,which reveals that they may co-act in the occurrence and development of OA.