Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, 215004, Suzhou, China.
Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 314000, Jiaxing, China.
Commun Biol. 2022 Jun 29;5(1):641. doi: 10.1038/s42003-022-03592-6.
Osteoarthritis (OA) is a highly prevalent and chronic disorder that is associated with a substantial social and economic burden. Itaconate, as an important regulator of cellular inflammation, is a metabolite synthesised by an enzyme encoded by immune-responsive gene 1. However, there are few studys regarding the effects of itaconate on OA. Here, we show the effect of the cell-permeable itaconate derivative 4-octyl itaconate (OI) on OA. OI attenuates the chondrocyte apoptosis induced by interleukin 1β (IL-1β) in vitro, indicating that OI protect chondrocytes against apoptosis. Moreover, OI ameliorates the chondrocyte autophagy inhibition induced by IL-1β via the inhibition of PI3K/AKT/mTOR signalling pathway. Finally, OI enhances autophagy and reduces cartilage degradation in a rat model of OA established by destabilization of medial meniscus (DMM). In summary, our findings reveal that OI is involved in regulating the progression of OA. The above results shed light on the treatment of OA.
骨关节炎（OA）是一种高发的慢性疾病，与巨大的社会和经济负担相关。衣康酸作为细胞炎症的重要调节剂，是由免疫反应基因 1 编码的酶合成的一种代谢物。然而，关于衣康酸对 OA 的影响的研究很少。在这里，我们展示了细胞通透的衣康酸衍生物 4-辛基衣康酸（OI）对 OA 的作用。OI 可减轻白细胞介素 1β（IL-1β）诱导的软骨细胞凋亡，表明 OI 可保护软骨细胞免受凋亡。此外，OI 通过抑制 PI3K/AKT/mTOR 信号通路改善了 IL-1β 诱导的软骨细胞自噬抑制。最后，OI 增强了自噬并减少了通过内侧半月板不稳定（DMM）建立的 OA 大鼠模型中的软骨降解。总之，我们的研究结果表明 OI 参与调节 OA 的进展。上述结果为 OA 的治疗提供了思路。
