罗格列酮通过抑制RANKL及p-ERK活化抑制类风湿关节炎破骨细胞的分化及功能  

Rosiglitazone inhibits osteoclastogenesis in rheumatoid arthritis by downregulating RANKL expression and suppressing ERK phosphorylation

作　　者：韦秀宁[1] 郑东辉[1] 莫颖倩[1] 马剑达[1] 戴冽[1] 

机构地区：[1]中山大学孙逸仙纪念医院风湿免疫科,广东广州510120

出　　处：《中国病理生理杂志》2015年第5期911-916,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81471597);高等学校博士学科点专项科研基金资助项目(No.20130171110075);广东省自然科学基金资助项目(No.2014A030313074)

摘　　要：目的:探讨罗格列酮(RSG)对类风湿关节炎(RA)成纤维样滑膜细胞(FLS)介导的破骨细胞(Oc)分化及功能的影响及其可能机制。方法:活动期RA患者滑膜体外分离培养FLS,与健康人外周血单核细胞(MNC)共培养,不同浓度RSG(0、5、10和15μmol/L)干预,抗酒石酸酸性磷酸酶(TRAP)染色鉴定Oc并计数;甲苯胺蓝染色和图像分析系统计算骨吸收陷窝面积;Real-time PCR检测共培养体系RANKL和OPG的mRNA表达,Western blot检测RANKL、OPG、p-ERK、p-p38和p-JNK的蛋白含量。结果:与不加RSG组比较,15μmol/L RSG干预后Oc的数量明显减少(P<0.01),骨吸收陷窝面积也减少(P<0.05);共培养体系RANKL的mRNA及蛋白表达明显降低,OPG的mRNA及蛋白表达明显升高(P<0.01);p-ERK的蛋白含量明显降低(P<0.05),p-p38及p-JNK的蛋白含量则不受影响。结论:RSG通过抑制RANKL及p-ERK活化影响RA关节微环境中组织细胞与免疫细胞的相互作用,从而抑制Oc分化及骨吸收功能。AIM： To investigate the effects of rosiglitazone on fibroblast-like synoviocyte （ FLS ）-induced osteoclastogenesis in rheumatoid arthritis （ RA） and the related mechanism.METHODS： RA-FLS were cocultured with peripheral blood monocytes from healthy volunteers in the presence of macrophage colony-stimulating factor （ M-CSF） and rosiglitazone.Osteoclasts were assayed by tartrate-resistant acid phosphatase （ TRAP） staining.Resorption lacunae area was identified by toluidine blue staining and quantified by image analysis software.The mRNA expression of RANKL and OPG was evaluated by real-time PCR, and the protein levels of RANKL, OPG, p-ERK, p-p38 and p-JNK were measured by Western blot.RESULTS：Compared with control group （ without rosiglitazone treatment） , rosiglitazone at concentration of 15 μmol/L significantly decreased the number of osteoclasts （P0.05 ） . CONCLUSION：Rosiglitazone inhibits RA-FLS-induced osteoclast formation and its resorption activity by down-regulating RANKL expression and ERK phosphorylation, suggesting that rosiglitazone may inhibit RA osteoclastogenesis and bone re-sorption.

关 键 词：类风湿关节炎 成纤维样滑膜细胞 破骨细胞 核因子ΚB受体活化因子配体 过氧化物酶体增殖物活化受体Γ 

分 类 号：R363.2[医药卫生—病理学] R593.22[医药卫生—基础医学]