Savaid Stomatology School, Hangzhou Medical College, Hangzhou, Zhejiang 310053, P.R. China.
Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang 310011, P.R. China.
Int J Mol Med. 2021 Mar;47(3). doi: 10.3892/ijmm.2020.4840. Epub 2021 Jan 15.
Osteoarthritis (OA) is a common joint disorder, and the restoration of the impaired cartilage remains a main concern for researchers and clinicians. MicroRNAs (miRNAs or miRs) play crucial roles in the pathogenesis of OA. The present study examined the therapeutic efficacy of exosomal‑miR‑140‑5p for the treatment of OA using dental pulp stem cells (DPSCs). The findings indicated that the exosomal burden of miR‑140‑5p was substantially increased following the transfection of DPSCs with miR‑140‑5p mimic. The administration of DPSC‑derived exosomes promoted chondrocyte‑related mRNA expression, including aggrecan, Col2α1 and Sox9, in interleukin (IL)‑1β‑treated human chondrocytes. This effect was substantially enhanced by miR‑140‑5p‑enriched exosomes. The results further revealed that miR‑140‑5p‑enriched exosomes induced a more significant reduction in IL‑1β‑induced chondrocyte apoptosis than the DPSC‑derived exosomes. Mechanistically, it was found that miR‑140‑enriched DPSC‑derived exosomes exerted anti‑apoptotic effects, probably by regulating the expression levels of apoptosis‑related proteins. Furthermore, multiple administrations of miR‑140‑5p‑enriched exosomes substantially improved knee joint conditions in a rat model of OA. Collectively, the data of the present study suggest that exosomes derived from genetically modified DPSCs may prove to be a potential strategy for the treatment of OA.
骨关节炎(OA)是一种常见的关节疾病,研究人员和临床医生仍然主要关注受损软骨的修复。MicroRNAs(miRNAs 或 miRs)在 OA 的发病机制中发挥着关键作用。本研究使用牙髓干细胞(DPSCs)研究了外泌体 miR-140-5p 治疗 OA 的疗效。研究结果表明,在 DPSCs 转染 miR-140-5p 模拟物后,miR-140-5p 的外泌体负担大大增加。DPSC 衍生的外泌体给药促进了白细胞介素(IL)-1β处理的人软骨细胞中软骨细胞相关 mRNA 的表达,包括聚集蛋白聚糖、Col2α1 和 Sox9。富含 miR-140-5p 的外泌体显著增强了这种作用。结果进一步表明,富含 miR-140-5p 的外泌体诱导的 IL-1β诱导的软骨细胞凋亡减少程度显著高于 DPSC 衍生的外泌体。从机制上讲,发现富含 miR-140 的 DPSCs 衍生的外泌体通过调节凋亡相关蛋白的表达水平发挥抗凋亡作用。此外,多次给予富含 miR-140-5p 的外泌体可显著改善 OA 大鼠模型的膝关节状况。综上所述,本研究的数据表明,遗传修饰的 DPSCs 衍生的外泌体可能被证明是治疗 OA 的一种有前途的策略。