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.

已知亚精胺抑制促炎细胞因子的产生。然而，没有关于亚精胺对骨关节炎（OA）的抗炎作用的报道。本文中，我们检查了在前十字韧带横断（ACLT）和TNF-α诱导的关节炎（TIA）小鼠模型中，腹膜内注射（ip）亚精胺是否可以延迟OA进展。在此过程中，人类FLS细胞（H-FLS）用于研究亚精胺介导的RIP1在TNF-α诱导的NF-κB/ p65信号传导中的潜在泛素化机制。我们发现，在用亚精胺治疗的ACLT和TIA小鼠中，亚精胺可减轻滑膜炎，软骨变性和骨赘形成，从而导致OARSI评分和TNF-α评分大大降低。就机理而言，9μM亚精胺不影响生存能力，增殖，细胞周期和H-FLS的凋亡，并通过激活CYLD介导的RIP1去泛素化对TNF-α诱导的H-FLS信号转导而发挥抑制作用。从这些数据，我们可以得出结论，亚精胺通过FLS中RIP1的去泛素化作用抑制TNF-α诱导的NF-κB通路，从而减弱OA进程。因此，摄入亚精胺可能是预防OA的潜在疗法。