Skeletal muscle-derived exosome-mediated regulation of bone formation and role of exercise intervention

Lu Biqiong; Wei Zhongjian

doi:10.12307/2026.340

Abstract：BACKGROUND:Abnormal bone formation is one of the primary causes of increased fracture risk and decreased quality of life.Skeletal muscle,as an important secretory organ,produces skeletal muscle-derived exosomes,which are closely related to bone formation.Recent studies have shown that exercise may regulate bone formation by modulating the secretion of skeletal muscle-derived exosomes.Therefore,a thorough investigation into the role and mechanisms of skeletal muscle-derived exosomes in regulating bone formation is of significant importance for improving quality of life and reducing fracture risk. OBJECTIVE:To summarize the role of skeletal muscle-derived exosomes in bone formation and their potential mechanisms,particularly the regulatory effects of exercise intervention on skeletal muscle-derived exosomes,providing new insights for the treatment of abnormal bone formation. METHODS:We searched the CNKI and PubMed databases using Chinese and English search terms"exosome,skeletal muscle-derived exosomes,bone formation,osteoblast,exercise."We screened relevant literature published between database inception and November 2024.Based on the relevance,quality,and suitability of the research content,we ultimately included 81 relevant articles for review. RESULTS AND CONCLUSION:(1)Current multi-omics,histological,and molecular biology studies have identified that miR-1,miR-133a,miR-133b,miR-206,and miR-27 in skeletal muscle-derived exosomes,as well as heat shock proteins,insulin-like growth factor binding protein 5,myotilin,and mesoderm paired homeobox protein 2,regulate osteogenic differentiation through the Wnt/β-catenin,bone morphogenetic protein 2 and Runt-related transcription factor 2,and other signaling pathways,improving osteoporosis.(2)Different types,intensities,and durations of exercise interventions have varying effects on the regulation of skeletal muscle-derived exosome release and their role in bone metabolism.However,due to the complexity of in vivo exosome tracking and identification,it is still difficult to precisely identify the source of circulating exosome after exercise.Future research needs to further explore the specific mechanisms.In summary,the role of skeletal muscle-derived exosomes in bone metabolism is increasingly recognized,and exercise intervention,by regulating exosome release,offers new possibilities for the treatment of bone metabolic diseases.