TRAF3抑制IL-17引起的软骨破坏作用  

Effects of TRAF3 on inhibiting cartilage breakdown induced by IL-17

作　　者：张宁[1] 刘宏强[2] 赵小英[1] 童文学[1] 张晓玲[1,3] 

机构地区：[1]上海交通大学医学院中科院上海生命科学研究院健康科学研究所骨科细胞与分子生物学实验室,上海200025 [2]山西大学体育学院,太原030006 [3]上海交通大学医学院附属第九人民医院骨科上海市骨科内植物重点实验室,上海200011

出　　处：《上海交通大学学报（医学版）》2014年第7期984-989,996,共7页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市科委国际合作项目(12410708600);上海交通大学"医工交叉研究基金"项目(YG2012ZD09);上海交通大学晨星青年学者奖励计划(2013SMC-A-6);上海教委重点学科建设基金(J50206)~~

摘　　要：目的研究肿瘤坏死因子受体相关因子3(TRAF3)对白介素-17(IL-17)刺激的软骨细胞中丝裂原激活蛋白激酶(MAPK)和核因子κB(NF-κB)信号通路及其下游产物表达的影响;观察TRAF3转基因小鼠IL-17刺激的关节软骨破坏情况,探讨TRAF3的软骨保护作用。方法 Western blotting检测正常软骨细胞和TRAF3基因过表达软骨细胞中IL-17刺激的MAPK和NF-κB信号通路的变化,Real-Time PCR检测正常软骨细胞和TRAF3基因过表达软骨细胞中IL-17刺激的下游炎症因子IL-6、基质金属蛋白酶-13(MMP13)、含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-4(ADAMTS-4)和ADAMTS-5 mRNA的表达变化,组织化学技术观察注射IL-17野生型小鼠与TRAF3转基因小鼠关节软骨变化的差异。结果 TRAF3的过表达能显著抑制经IL-17刺激软骨细胞中MAPK和NF-κB信号通路,使下游炎症因子IL-6、MMP13、ADAMTS-4和ADAMTS-5 mRNA的表达显著下调;TRAF3转基因小鼠IL-17引起的关节软骨降解显著较野生型小鼠减轻。结论作为IL-17信号通路的负调控抑制剂,TRAF3可能成为抑制关节炎软骨破坏的新靶点。Objective To investigate the effects of TNF receptor associated factor 3 （TRAF3） on signaling pathways and expressions of downstream products of MAPK and NF-κB in chondrocytes stimulated by the interleukin-17 （IL-17） ; to observe the cartilage destruction of TRAF3 transgenic mice stimulated by the IL-17; and to explore the protective effect of TRAF3 on the cartilage. Methods Changes of signaling pathways of NF-κB and MAPK in normal chondrocytes and TRAF3 transgenic chondrocytes stimulated by the IL-17 were detected by the Western blotting. The changes of mRNA of downstream inflammatory factor IL-6, metabolic factors MMP13, disintegrin and metalloproteinase with thrombospondin motif4 （ADAMTS-4）, and ADAMTS- 5 in normal chondrocytes and TRAF3 transgenic chondrocytes stimulated by the IL-17 were detected by the Real-Time PCR. Differences of cartilage changes of wildtype mice and TRAF3 transgenic mice stimulated by the IL-17 were observed by the histochemistry. Results The over-expression of TRAF3 significandy inhibited the signaling pathways of MAPK and NF-κB in chondrocytes stimulated by the IL-17 and significantly down- regulated the expression of mRNA of downstream inflammatory factors IL-6, MMP13, ADAMTS-4, and ADAMTS. The cartilage breakdown of TRAF3 transgenic mice induced by the IL-17 was significandy less than that of wildtype mice. Conclusion TRAF3 is a negative regulatory inhibitor of the signaling pathways of IL-17 and may be a new target of inhibiting the cartilage breakdown.

关 键 词：肿瘤坏死因子受体相关因子3 白介素-17 炎症 软骨保护 

分 类 号：R681.3[医药卫生—骨科学]