| RRC ID |
63769
|
| 著者 |
Hu G, Zhang N, Li J, Wang J, Wu W, Li J, Tong W, Zhao X, Dai L, Zhang X.
|
| タイトル |
Tumor Necrosis Factor Receptor Associated Factor 3 Modulates Cartilage Degradation through Suppression of Interleukin 17 Signaling.
|
| ジャーナル |
Am J Pathol
|
| Abstract |
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-κB 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.
|
| 巻・号 |
190(8)
|
| ページ |
1701-1712
|
| 公開日 |
2020-8-1
|
| DOI |
10.1016/j.ajpath.2020.04.016
|
| PII |
S0002-9440(20)30239-X
|
| PMID |
32416098
|
| MeSH |
Animals
Arthritis, Experimental / genetics
Arthritis, Experimental / metabolism*
Arthritis, Experimental / pathology
Cartilage, Articular / metabolism*
Cartilage, Articular / pathology
Chondrocytes / metabolism
Chondrocytes / pathology
Interleukin-17 / metabolism*
Mice
Mice, Transgenic
NF-kappa B / metabolism
Osteoarthritis / genetics
Osteoarthritis / metabolism*
Osteoarthritis / pathology
Signal Transduction / physiology*
TNF Receptor-Associated Factor 3 / genetics
TNF Receptor-Associated Factor 3 / metabolism*
|
| IF |
3.491
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
