論文 - 詳細
| RRC ID | 62927 |
|---|---|
| 著者 | Chen Z, Lin CX, Song B, Li CC, Qiu JX, Li SX, Lin SP, Luo WQ, Fu Y, Fang GB, Wei-Ping L, Saw PE, Ding Y. |
| タイトル | Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis. |
| ジャーナル | Cell Death Dis |
| Abstract |
Spermidine has been known to inhibit the production of pro-inflammatory cytokines. However, there are no reports about anti-inflammatory effects of spermidine on osteoarthritis (OA). Herein, we examined whether OA progression could be delayed by intraperitoneal injection (i.p.) of spermidine in the anterior cruciate ligament transection (ACLT) and TNF-α induced arthritis (TIA) mouse models. During the process, human FLS cells (H-FLS) were used to investigate the potential ubiquitination mechanism of spermidine-mediated RIP1 in TNF-α-induced NF-κB/p65 signaling. We found that spermidine attenuated synovitis, cartilage degeneration and osteophyte formation, resulting in substantially lower OARSI scores and TNF-α scores in spermidine-treated ACLT and TIA mice. In terms of the mechanism, 9 μM spermidine did not affect the viability, proliferation, cell cycle and apoptosis of H-FLS, and exerted inhibitory effects by activating CYLD-mediated RIP1 deubiquitination on TNF-α-induced NF-κB/p65 signaling in H-FLS. From these data, we can conclude that spermidine attenuates OA progression by the inhibition of TNF-α-induced NF-κB pathway via the deubiquitination of RIP1 in FLS. Therefore, intake of spermidine could be a potential therapy for preventing OA. |
| 巻・号 | 11(7) |
| ページ | 503 |
| 公開日 | 2020-7-6 |
| DOI | 10.1038/s41419-020-2710-y |
| PII | 10.1038/s41419-020-2710-y |
| PMID | 32632306 |
| PMC | PMC7338517 |
| MeSH | Animals Anterior Cruciate Ligament Injuries / pathology Cartilage, Articular / drug effects Cartilage, Articular / pathology Cell Line Deubiquitinating Enzyme CYLD / metabolism Disease Models, Animal GTPase-Activating Proteins / metabolism* Humans Inflammation / pathology Male Mice, Inbred C57BL Models, Biological NF-kappa B / genetics NF-kappa B / metabolism* Nuclear Pore Complex Proteins / metabolism* Osteoarthritis / metabolism* Osteoarthritis / pathology RNA-Binding Proteins / metabolism* Signal Transduction* Spermidine / pharmacology* Synovial Membrane / pathology Transcription Factor RelA / metabolism* Tumor Necrosis Factor-alpha Ubiquitination* / drug effects |
| IF | 6.304 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 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) |