M1-Derived Migrasome Ameliorate Temporomandibular Joint Osteoarthritis Via Autophagy Activation

Emerging evidence highlights migrasomes as critical mediators of intercellular communication through their ability to shuttle bioactive cargo—including signaling molecules, proteases, and genetic material. Considering that M1 macrophages have a high capacity to produce large numbers of migrasomes, and play essential role in pathogenesis of OA, we wonder whether migrasomes derived from M1 macrophages participate in the pathogenesis of TMJ-OA. We engineered a dual-chamber synovium-cartilage organoid coculture system and introduced a filtration device (with 0.3 μm and 200 nm filters) into the system to interfere with the inter-tissue transfer of migrasomes. TNF-α-induced chondrocyte degradation model (50 ng/ml, 24h) was used in in vitro experiments. MIA-induced arthritic rats were used for investigation in in vivo experiments In a TNF-α-induced chondrocyte degradation model, migrasome intervention selectively restored cell viability and proteoglycan synthesis by suppressing catabolic enzymes (e.g., MMP-13, ADAMTS-5) and reactivating chondrogenic programs. Organoid studies revealed that blocking migrasome transmission (via 200 nm filters) reduced LC3 and Beclin-1 expression while increasing P62 accumulation. Supplementing M1 macrophage-derived migrasomes reversed these effects, restoring autophagic markers. Translational validation in a rat TMJ-OA model showed intra-articular migrasome administration attenuated condylar degeneration, improving bone microarchitecture and cartilage integrity. Mechanistically, migrasomes counteracted TNF-α-induced catabolism by restoring autophagic flux, with concordant organoid and in vivo outcomes highlighting autophagy activation as the core chondroprotective mechanism. M1 macrophage-derived migrasomes alleviate joint inflammation by activating chondrocyte autophagy