Synovial inflammatory macrophage-derived extracellular vesicles exacerbate cartilage lesions with a FMRP-selectively sorted manner in osteoarthritis.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Osteoarthritis (OA) is an aging-related degenerative joint disease without effective therapies. In the early stage of OA, mild synovitis has been reported to induce cartilage lesions. A better understanding of crosstalk between synovial macrophages and chondrocytes are being developed to discover new OA therapeutics. Here, we identified that the extracellular vesicles (EVs) derived from synovial pro-inflammatory macrophages regulated the autophagy function of chondrocytes, induced the onset of cartilage degeneration in normal joints. Mechanistically, the active transfer of miR-155-5p via EVs from synovial pro-inflammatory macrophages to chondrocytes accelerates cartilage degeneration by suppressing GSK-3β/mTORC1 axis-mediated autophagy function during OA progression. Deleting miR-155 from synovial pro-inflammatory macrophages relieved cartilage lesions and synovitis in OA mice. On the other hand, Fragile X mental retardation protein (FMRP) selectively sorted miR-155-5p into EVs derived from synovial pro-inflammatory macrophages, and the levels of plasma EVs FMRP were closely related to OA progression, suggesting the potential candidate for diagnostic OA biomarkers. Based on these findings, we developed engineering EVs with MAP (pro-inflammatory macrophages-affinity peptide) derived from adipose-derived stromal cells (ADSCs) as the antagomiR-155-5p delivery vehicles which exhibi

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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