The CXCR4/SDF1 axis improves muscle regeneration through MMP-10 activity

This study demonstrates that the CXCR4/SDF1 signaling axis is essential for efficient skeletal muscle regeneration after injury. CXCR4 and its ligand SDF1 are up-regulated in damaged muscle, and pharmacological inhibition of CXCR4 or siRNA-mediated depletion of CXCR4 or SDF1 delays regeneration, reduces the number of newly formed eMyHC-positive myofibers, and alters satellite cell dynamics, leading to increased proliferation but impaired differentiation and repair. Conversely, exogenous SDF1 accelerates muscle repair in vivo and enhances satellite cell–derived myoblast proliferation, fusion, and myotube growth in vitro. Importantly, the regenerative effects of the CXCR4/SDF1 axis depend on matrix metalloproteinase-10 (MMP-10): genetic deletion or silencing of MMP-10 reduces CXCR4 and SDF1 expression and abolishes both the pro-regenerative effect of SDF1 and the inhibitory effect of CXCR4 blockade in injured muscle. The authors conclude that MMP-10 functionally modulates CXCR4/SDF1 signaling to coordinate satellite cell behavior and muscle repair, identifying this pathway as a potential therapeutic target for muscle injury and degenerative diseases.