The interaction between synovial cells and chondrocytes plays a pivotal role in the progression of osteoarthritis. However, the contribution of migrasomes, recently identified vesicular organelles mediating intercellular communication, remains inadequately explored in this context. Here, we first confirmed the presence of migrasomes in both synovial tissues and synovial fluid samples from patients with temporomandibular joint osteoarthritis (TMJ-OA). Integrative analyses, combining single-cell transcriptomics with in vitro validation, identified infiltrating M1 macrophages as one of the major sources of synovial migrasomes. Notably, M1 macrophage-derived migrasomes alleviated TNF-α-induced chondrocyte apoptosis, reduced proteoglycan depletion, and suppressed the expression of catabolic enzymes. Further analyses revealed that these migrasomes were enriched in autophagy-related proteins, implicating a link between migrasomes and autophagy. Using a synovium-cartilage organoids co-culture model (“Mini-TMJ”), we observed that blocking migrasome transfer from the synovial to the cartilage organoid led to reduced autophagy activation in the cartilage organoid under monosodium iodoacetate-induced inflammatory conditions. Conversely, exogenous addition of M1 macrophage-derived migrasomes into the cartilage organoid restored autophagy activity. In a rat TMJ-OA model, intra-articular injection of M1 macrophage-derived migrasomes effectively attenuated cartilage degradation and promoted autophagy activation. Collectively, our findings indicate that M1 macrophage-derived migrasomes ameliorate TMJ-OA progression by enhancing autophagy.
Sa et al. (Tue,) studied this question.