Department of Blood Transfusion, Yantai Yuhuangding Hospital, Yantai, Shandong, China.
Pharmacy Intravenous Admixture Services, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, Shandong, China.
J Musculoskelet Neuronal Interact. 2024 Dec 1;24(4):409-419.
To elucidate how indomethacin may slow the progression of osteoarthritis (OA).
Chondrocytes were treated with IL-1β (10 ng/mL) for 12 hours to create an in vitro model of OA. Following this, 10 μM of indomethacin was added to the IL-1β-treated chondrocytes for an additional 4 hours to evaluate its effects on inflammation, anabolism, catabolism, apoptosis, and autophagy using ELISA, western blot, immunofluorescence and flow cytometry, respectively.
IL-1β significantly stimulated inflammatory responses, hampered anabolic processes, induced catabolic activity, accelerated apoptosis, and inhibited autophagy in chondrocytes, as well as activated the PI3K/AKT/mTOR signaling pathway. However, treatment with indomethacin reversed the effects of IL-1β stimulation on chondrocytes and simultaneously suppressed the activation of the PI3K/AKT/mTOR signaling pathway.
Our findings indicate the mechanism of action of indomethacin in mitigating OA progression, indicating that it can inactivate the PI3K/AKT/mTOR signaling pathway, thereby regulating inflammation, metabolism, apoptosis, and autophagy in chondrocytes, which attenuates the development of OA.
阐明吲哚美辛如何减缓骨关节炎（OA）的进展。
用白细胞介素 1β（10ng/ml）处理软骨细胞 12 小时，以建立 OA 的体外模型。然后，将 10μM 吲哚美辛添加到 IL-1β 处理的软骨细胞中 4 小时，以分别使用 ELISA、western blot、免疫荧光和流式细胞术评估其对炎症、合成代谢、分解代谢、细胞凋亡和自噬的影响。
IL-1β 显著刺激炎症反应，阻碍合成代谢过程，诱导分解代谢活性，加速软骨细胞凋亡，抑制自噬，并激活 PI3K/AKT/mTOR 信号通路。然而，吲哚美辛治疗逆转了 IL-1β 刺激对软骨细胞的影响，同时抑制了 PI3K/AKT/mTOR 信号通路的激活。
我们的研究结果表明吲哚美辛在减轻 OA 进展中的作用机制，表明它可以使 PI3K/AKT/mTOR 信号通路失活，从而调节软骨细胞中的炎症、代谢、细胞凋亡和自噬，从而减缓 OA 的发展。
