The Dual Role of Small Extracellular Vesicles in Joint Osteoarthritis: Their Global and Non-Coding Regulatory RNA Molecule-Based Pathogenic and Therapeutic Effects.

OA is the most common joint disease that affects approximately 7% of the global population. Current treatment methods mainly relieve its symptoms with limited repairing effect on joint destructions, which ultimately contributes to the high morbidity rate of OA. Stem cell treatment is a potential regenerative medical therapy for joint repair in OA, but the uncertainty in differentiation direction and immunogenicity limits its clinical usage. Small extracellular vesicles (sEVs), the by-products secreted by stem cells, show similar efficacy levels but have safer regenerative repair effect without potential adverse outcomes, and have recently drawn attention from the broader research community. A series of research works and reviews have been performed in the last decade, providing references for the application of various exogenous therapeutic sEVs for treating OA. However, the clinical potential of target intervention involving endogenous pathogenic sEVs in the treatment of OA is still under-explored and under-discussed. In this review, and for the first time, we emphasize the dual role of sEVs in OA and explain the effects of sEVs on various joint tissues from both the pathogenic and therapeutic aspects. Our aim is to provide a reference for future research in the field.