ReferenceID 2879
Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis
Cell Death Dis
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 progre
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Record Fields
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- Reference Id
- 2879
- Evidence Id
- 19469
- Core Evidence Id
- 19469
- Source Reference Id
- 5744
- Herb2 Reference Id
- HBREF006541
- Subject Paper Key
- HBIN044493_32632306
- Pubmed Id
- 32632306
- Doi
- 10.1038/s41419-020-2710-y
- Paper Title
- Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis
- Paper 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-alpha 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-alpha-induced NF-kappaB/p65 signaling. We found that spermidine attenuated synovitis, cartilage degeneration and osteophyte formation, resulting in substantially lower OARSI scores and TNF-alpha scores in spermidine-treated ACLT and TIA mice. In terms of the mechanism, 9 muM 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-alpha-induced NF-kappaB/p65 signaling in H-FLS. From these data, we can conclude that spermidine attenuates OA progression by the inhibition of TNF-alpha-induced NF-kappaB pathway via the deubiquitination of RIP1 in FLS. Therefore, intake of spermidine could be a potential therapy for preventing OA.
- Journal
- Cell Death Dis
- Publish Year
- 2020
- Experiment Subject
- mouse; human; human fls cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Synovitis; Osteoarthritis; Osteophyte; Anterior Cruciate Ligament Transection; Arthritis; Cartilage Degeneration
- Paper Title Cn
- Paper Title En
- Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis
- Bilingual Status
- semi_complete