Deer antler ASCs exosomes ameliorate osteoarthritis via miR-140/MMP13 axis-mediated dual modulation of inflammation and cartilage regeneration

Osteoarthritis (OA) is a progressive joint disease characterized by cartilage degeneration. Although the current use of mesenchymal stromal cells (MSCs) treatment provides a novel therapeutic option, stem cell therapy is limited to the risk of immune rejection, and stem cell-derived extracellular vesicles (Exos) are emerging as a more potential choice. Antler is a truly regenerative organ with unprecedented regenerative capacity and chondrogenic potential, and its derived antler stem cells (ASCs) provide a unique and sustainable biological resource for obtaining bioactive ASC-Exos. In this study, we found that intra-articular injection of ASC-Exos can effectively promote cartilage repair. Further analysis indicated that the key functional component of these exosomes is mir-140, which functions by regulating its target, matrix metalloproteinase 13 (MMP13). Finally, we found that miR-140-engineered ASC-Exo promotes chondrocyte activity, reduces apoptosis both in vitro and in vivo, and alleviates inflammation while inhibiting cartilage matrix degradation. Therefore, this study provides a new regenerative medical strategy for the treatment of osteoarthritis.