| 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
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
