Exosome-mediated muscle-bone crosstalk: mechanisms and therapeutic potential

Muscle and bone maintain homeostasis through biomechanical and molecular crosstalk. Disruption of this interaction leads to osteosarcopenia, a condition marked by concurrent muscle and bone loss. Exosomes carry proteins and nucleic acids between tissues and are now recognized as key mediators of intercellular communication. Clarifying the role of exosomes in muscle-bone crosstalk is essential for identifying new biomarkers and therapeutic targets for musculoskeletal diseases. This review first summarizes the biogenesis and molecular composition of exosomes. It then examines the regulatory effects of skeletal muscle-derived exosomes on bone metabolism, focusing on how myogenic miRNAs and proteins influence osteoblast and osteoclast activity. The review also addresses the reverse pathway, describing how bone-derived exosomes, particularly those from BMSCs, affect myogenesis and muscle atrophy. We further assess their translational potential as circulating biomarkers, therapeutic delivery vehicles, and engineered platforms, while considering current limitations in isolation and characterization, biodistribution, manufacturing, safety, and regulatory oversight. Exosomes are critical mediators of muscle-bone crosstalk, with their cargo reflecting the physiological state of source cells. While exosome-based tools show promise for the diagnosis and treatment of conditions like osteosarcopenia, challenges remain in standardizing preparation methods and achieving tissue-specific delivery. Future work integrating multi-omics and artificial intelligence will be necessary to translate these findings into clinical applications for musculoskeletal health.