Human umbilical cord mesenchymal stem cell-derived extracellular vesicles attenuate osteoarthritis via LncRNA BCYRN1-mediated activation of autophagy associated with the hsa-miR-6842-5p/MAPK13 axis

Extracellular vesicles from mesenchymal stem cells (MSC-EVs) are being explored for osteoarthritis (OA) treatment, but how they work is not fully understood. In this study, we looked at extracellular vesicles from human umbilical cord MSCs (HuMSCs-EVs) and their effects on OA. Treatment with HuMSCs-EVs boosted the expression of cartilage-related genes and lowered the levels of inflammatory genes. LncRNA sequencing pointed to BCYRN1 as a key functional component inside these extracellular vesicles. Further experiments showed that BCYRN1 delivered by HuMSCs-EVs directly binds and suppresses hsa-miR-6842-5p, which in turn releases MAPK13, potentially contributing to autophagy in OA chondrocytes. This was supported by increased autophagosome formation and higher levels of autophagy-related proteins. Knocking down BCYRN1 blocked these effects, while overexpressing BCYRN1 made them stronger. In vivo model of OA, injecting BCYRN1-enriched HuMSCs-EVs into the joint clearly reduced cartilage damage and inflammatory protein levels. In contrast, BCYRN1-deficient HuMSCs-EVs failed to show any benefit. Together, our results reveal a functional axis involving BCYRN1/miR-6842-5p/MAPK13, that is closely associated with the autophagy pathway and the protective effects of HuMSCs-EVs on cartilage, and suggest that loading BCYRN1 into extracellular vesicles could be a promising cell-free therapy for OA.