The bone-muscle unit: from mechanical coupling to soluble factors-mediated signaling

Skeletal muscles (SKM) and bones form a morpho-functional unit, interconnected throughout life primarily through biomechanical coupling. This relationship serves as a key reciprocal stimulus, but they also interact via various hormones, such as sex steroids, growth hormone-insulin-like growth factor 1 (GH-IGF1) axis hormones, and adipokines like leptin and adiponectin. Additionally, myokines (released by muscles) and osteokines (released by bones) facilitate dense crosstalk, influencing each other's activity. Key myokines include interleukin (IL)-6, IL-7, IL-15, and myostatin, while osteocalcin (OC) and sclerostin are crucial bone-derived mediators affecting SKM cells. Moreover, miRNAs act as endocrine-like regulators, contributing to a complex network. This review covers the current understanding of bone-muscle crosstalk, which is essential for grasping the musculoskeletal apparatus's role in disease pathogenesis and may inform therapeutic development.