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.Keywords: osteoarthritis; microRNAs; exosomal‑miR‑140‑5p; dental pulp stem cells; apoptosis.