Inhibition of chondrocyte apoptosis in a rat model of osteoarthritis by exosomes derived from miR‑140‑5p‑overexpressing human dental pulp stem cells

• Published in: International journal of molecular medicine 2021-03, Vol.47 (3), p.1-10, Article 7
• Main Authors: Lin, Tianji, Wu, Nan, Wang, Linhong, Zhang, Ruipeng, Pan, Ruolang, Chen, Yun-Fang
• Format: Article
• Language: English
• Subjects: Apoptosis; Arthritis; Cartilage; Dental pulp; Gene expression; Growth factors; Injuries; Laboratory animals; MicroRNAs; Osteoarthritis; Stem cells
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2020.4840

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.