Mechanism of Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Matrix for Articular Cartilage Repair

Abstract

Articular cartilage injuries present a significant clinical challenge due to the tissue's limited self-repair capacity and the inadequacy of current regenerative strategies. This study aimed to investigate whether bone marrow mesenchymal stem cell-derived extracellular matrix (BM–ECM) enhances cartilage repair and to elucidate the underlying molecular mechanisms involving ubiquitin-specific protease 7 (USP7). Rat BMSCs were isolated and characterized, and decellularized BM–ECM was prepared. Cartilage defects in a rat model were treated with GelMA hydrogel scaffolds loaded with BMSCs and BM–ECM. Histological evaluation demonstrated that the BM–ECM composite scaffold significantly improved cartilage repair. Further mechanistic investigation revealed that BM–ECM promoted chondrogenic differentiation of BMSCs, an effect closely associated with USP7 activity. Overexpression of USP7 enhanced ECM synthesis and chondrogenesis, whereas USP7 knockdown diminished these processes and abolished the prochondrogenic benefits of BM–ECM. In conclusion, BM–ECM facilitates cartilage regeneration, with USP7 playing a central role in mediating its chondro-supportive effects, offering a promising therapeutic target for cartilage repair.