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 Here, we identified miR‐126‐5p in BMSC‐derived exosomes as a positive regulator of muscle regeneration. These exosomes promoted the proliferation and maturation of myoblasts and facilitated the regeneration of skeletal muscle in male C57BL/6J mice. FBXO32 was confirmed as the downstream target of exosomal miR‐126‐5p to regulate skeletal muscle regeneration, and it ubiquitinated and degraded myogenic differentiation 1 (MyoD). Notably, miR‐126‐5p knockdown from BMSC‐derived exosomes significantly inhibited proliferation and differentiation of Pax7 + 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.