| First Author | Hu G | Year | 2020 |
| Journal | Am J Pathol | Volume | 190 |
| Issue | 8 | Pages | 1701-1712 |
| PubMed ID | 32416098 | Mgi Jnum | J:293416 |
| Mgi Id | MGI:6452667 | Doi | 10.1016/j.ajpath.2020.04.016 |
| Citation | Hu G, et al. (2020) Tumor Necrosis Factor Receptor Associated Factor 3 Modulates Cartilage Degradation through Suppression of Interleukin 17 Signaling. Am J Pathol 190(8):1701-1712 |
| abstractText | Interleukin 17A (IL-17A) is critical in the pathogenesis of autoimmune diseases through driving inflammatory cascades. However, the role of IL-17 in osteoarthritis (OA) is not well understood. Tumor necrosis factor-receptor-associated factor 3 (TRAF3) is a receptor proximal negative regulator of IL-17 signaling. It remains unclear whether TRAF3 exerts regulatory effects on cartilage degradation and contributes to the pathogenesis of OA. In this study, we found that TRAF3 notably suppressed IL-17-induced NF-kappaB and mitogen-activated protein kinase activation and, subsequently, the production of matrix-degrading enzymes. TRAF3 depletion enhanced IL-17 signaling, along with increased matrix-degrading enzyme production. In vivo, cartilage destruction caused by surgery-induced OA was alleviated markedly both in 1l17a-deficient mice and in TRAF3 transgenic mice. In contrast, silencing TRAF3 through adenoviruses worsened cartilage degradation in experimental OA. Moreover, the destructive effect of IL-17 on cartilage was abolished in TRAF3 transgenic mice in an IL-17 intra-articular injection animal model. Similarly, genetic deletion of IL-17 blocked TRAF3 knockdown-mediated promotion of cartilage destruction, suggesting that the protective effect of TRAF3 on cartilage is mediated by its suppression of IL-17 signaling. Collectively, our results suggest that TRAF3 negatively regulates IL-17-mediated cartilage degradation and pathogenesis of OA, and may serve as a potential new therapy target for OA. |
