• Original article (Basic research) • Previous Articles     Next Articles

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

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