上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

TRAF3抑制IL-17引起的软骨破坏作用

张 宁1，刘宏强2，赵小英1，童文学1，张晓玲1,3   

  1. 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
  • 出版日期:2014-07-28 发布日期:2014-08-11
  • 通讯作者: 张晓玲, 电子信箱: xlzhang@sibs.ac.cn。
  • 作者简介:张 宁（1987—)， 男， 硕士生; 电子信箱: zhangning621@gmail.com。
  • 基金资助:

    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）

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

ZHANG Ning1, LIU Hong-qiang2, ZHAO Xiao-ying1, TONG Wen-xue1, ZHANG Xiao-ling1,3   

  1. 1.Laboratory of Orthopaedic Cell and Molecular Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China; 2.School of Physical Education, Shanxi University, Taiyuan 030006, China; 3.Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
  • Online:2014-07-28 Published:2014-08-11
  • Supported by:
    International Collaboration Programs by Science and Technology Commission of Shanghai Municipality,12410708600; Biomedical Engineering Cross Research Foundation of Shanghai Jiao Tong University, YG2012ZD09; Morning Star Young Scholars Program of Shanghai Jiao Tong University, 2013SMC-A-6; Key Discipline Construction Foundation of Shanghai Municipal Education Committee, J50206

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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。

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

Abstract:

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 hondrocytes 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 motif 4 (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 significantly 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 significantly 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.

Key words: tumor necrosis factor receptor associated factor 3, interleukin-17, inflammation, cartilage protection