Curcumin treatment was reported to delay the progression of OA, but its underlying mechanism remains unclear. In this study, we aimed to investigate the molecular mechanism underlying the role of curcumin in OA treatment. Accordingly, by conducting MTT and flow cytometry assays, we found that the exosomes derived from curcumin‐treated MSCs helped to maintain the viability while inhibiting the apoptosis of model OA cells. Additionally, quantitative real‐time PCR and Western blot assays showed that the exosomes derived from curcumin‐treated MSCs significantly restored the down‐regulated miR‐143 and miR‐124 expression as well as up‐regulated NF‐kB and ROCK1 expression in OA cells. Mechanistically, curcumin treatment decreased the DNA methylation of miR‐143 and miR‐124 promoters. In addition, the 3’ UTRs of NF‐kB and ROCK1 were proven to contain the binding sites for miR‐143 and miR‐124, respectively. Therefore, the up‐regulation of miR‐143 and miR‐124 in cellular and mouse OA models treated with exosomes remarkably restored the normal expression of NF‐kB and ROCK1. Consequently, the progression of OA was attenuated by the exosomes. Our results clarified the molecular mechanism underlying the therapeutic role of MSC‐derived exosomes in OA treatment.

中文翻译：

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姜黄素通过调节miR-124 / NF-kB和miR-143 / ROCK1 / TLR9信号通路来增强MSC衍生的外来体来减轻骨关节炎。

据报道姜黄素治疗可延迟OA的进展，但其潜在机制仍不清楚。在这项研究中，我们旨在研究姜黄素在OA治疗中的潜在分子机制。因此，通过进行MTT和流式细胞仪检测，我们发现姜黄素处理过的MSC产生的外泌体有助于维持活力，同时抑制了模型OA细胞的凋亡。此外，实时荧光定量PCR和Western blot分析表明，姜黄素处理过的MSC的外泌体显着恢复了OA细胞中miR-143和miR-124表达下调以及NF-kB和ROCK1表达上调。从机理上讲，姜黄素处理降低了miR-143和miR-124启动子的DNA甲基化。此外，已证明NF-kB和ROCK1的3'UTR分别包含miR-143和miR-124的结合位点。因此，在用外泌体处理的细胞和小鼠OA模型中，miR-143和miR-124的上调显着恢复了NF-kB和ROCK1的正常表达。因此，外泌体减弱了OA的进展。我们的结果阐明了MSC衍生的外泌体在OA治疗中的治疗作用的分子机制。