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

鹿茸脂肪干细胞外泌体通过miR-140/MMP13轴介导的炎症和软骨再生双重调节作用,改善骨关节炎

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作者:Yuhao Song #,Xue Wang #,Xinrui Yan,Xin Li,Xintong Han,Yu Zhang,Yusu Wang,Xinran Chen,Xinyi Li,Xinyu Zhang,Boyin Jia,Rui Du

Abstract

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.

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