MiR‐126‐5p Derived From Bone Marrow Mesenchymal Stem Cell Exosomes Promotes Skeletal Muscle Regeneration by Regulating FBXO32/MyoD Signaling

AIM: In the process of muscle growth and repair, microRNAs (miRNAs) serve as a critical factor in spatiotemporal regulation. Nevertheless, the molecular regulatory mechanisms underlying muscle regeneration remain largely unknown. METHODS: Exosomes from control and miR-126-knockdown BMSCs were isolated via ultracentrifugation. A mouse muscle injury model was established using 1.2% barium chloride in gastrocnemius muscles. Injured tissues received local injections of BMSC exosomes or AAV-miR-126. Gene expression was analyzed by qRT-PCR/Western blot. Tissue morphology and repair were assessed via H&E staining, while regeneration markers were evaluated through immunostaining. RESULTS: SCs and muscle regeneration, whereas adeno-associated virus (AAV)-mediated overexpression of miR-126-5p accelerated these processes. Specifically, the BMSC-derived exosomes delivered miR-126-5p to skeletal muscle, thus decreasing the expression of FBXO32, in turn increasing MyoD expression, finally significantly promoting satellite cell differentiation and skeletal muscle regeneration. CONCLUSIONS: BMSC-derived exosomes could promote skeletal muscle injury repair through miR-126-5p, and thus miR-126-5p may act as a molecular therapeutic target of skeletal muscle diseases. Elucidating functional mechanisms of exosomes and miRNA is of great significance for developing new biotherapy strategies for skeletal muscle disease.