MMP-10 is required for efficient muscle regeneration in mouse models of injury and muscular dystrophy

This study demonstrates that matrix metalloproteinase-10 (MMP-10) is a key regulator of skeletal muscle regeneration after acute injury and in Duchenne muscular dystrophy. MMP-10 expression is up-regulated in muscle following notexin-induced damage and in dystrophic mdx mice, and is detected in satellite cells and vascular cells. Mice lacking MMP-10 show impaired muscle regeneration, characterized by reduced endothelial cell recruitment, altered extracellular matrix composition, decreased collagen deposition, smaller regenerating fibers, and delayed formation of new myofibers after injury. Genetic ablation of MMP-10 in mdx mice further worsens the dystrophic phenotype, with increased muscle degeneration and reduced regenerative capacity. Conversely, local delivery of recombinant MMP-10 accelerates muscle repair, while MMP-10 silencing delays regeneration. Mechanistically, MMP-10 promotes efficient satellite cell–derived myoblast fusion and myotube growth and is associated with activation of VEGF/Akt signaling. Together, these findings identify MMP-10 as a critical mediator of muscle maintenance and regeneration during injury and muscular dystrophy.