論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |