Extracellular vesicles derived from synovial inflammatory macrophages induce the onset of osteoarthritis in a FMRP-selectively sorted manner

Osteoarthritis (OA) is an aging-related degenerative joint disease without effective therapeutic. In the early stage of OA, mild synovitis has been proven to induce normal cartilage lesions. However, the mechanism is poorly defined. Here, we identified that the extracellular vesicles (EVs) derived from synovial inflammatory macrophages regulate the autophagy function of chondrocytes, acting as the dominant inducer of the onset of cartilage degeneration in normal and OA joints. Mechanistically, the active transfer of miR-155-5p via EVs from synovial inflammatory macrophages to chondrocytes accelerates cartilage degeneration by suppressing GSK 3β/mTORC1 axis-mediated autophagy function during OA progression. To explore the underlying mechanism by which synovial inflammatory macrophages aggravate cartilage damage in OA progression, the miRNA expression in EVs derived from synovial macrophages between sham and OA rats was examined. As BM-derived macrophages contributed to the pool of synovial macrophages during OA progression, the CD45+ and CD11b+ monocytes from BM cells between sham and OA rats were sorted. Then the sorted monocytes were induced to M0 (presented synovial macrophages in the sham model) and M1 polarization (presented synovial inflammatory macrophages in the OA model), separately. The Agilent Rat miRNA Microarray, Release 21.0 (8*15K, Design ID: 070154) were used to investigated. The microarray has 758 probes for mature miRNAs of rats.