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.