Bone and muscle crosstalk in ageing and disease

Interorgan communication between bone and skeletal muscle is central to human health. A dysregulation of bone-muscle crosstalk is implicated in several age-related diseases. Ageing-associated changes in endocrine, inflammatory, nutritional and biomechanical stimuli can influence the differentiation capacity, function and survival of mesenchymal stem cells and bone-forming and muscle-forming cells. Consequently, the secretome phenotype of bone and muscle cells is altered, leading to impaired crosstalk and, ultimately, catabolism of both tissues. Adipose tissue acts as a third player in the bone-muscle interaction by secreting factors that affect bone and muscle cells. Physical exercise remains the key biological stimulus for bone-muscle crosstalk, either directly via the release of cytokines from bone, muscle or adipocytes, or indirectly through extracellular vesicles. Overall, bone-muscle crosstalk is considered an inherent process necessary to maintain the structure and function of both tissues across the life cycle. This Review summarizes the latest biomedical advances in bone-muscle crosstalk as it pertains to human ageing and disease. We also outline future research priorities to accommodate the understanding of this rapidly emerging field.