The skeletal muscle secretome: an emerging player in muscle-bone crosstalk

In vitro and in vivo studies provide evidence that a variety of growth factors and cytokines are actively secreted by muscle tissue. Muscle can therefore function as an endocrine and paracrine organ. These peptides characterize the muscle secretome, and many muscle-derived factors such as insulin-like growth factor-1, basic fibroblast growth factor, interleukin-15, myostatin and secreted protein acidic and rich in cysteine (osteonectin) are also known to have significant effects on bone metabolism. The factors secreted by muscle may vary according to muscle activity, in that muscle contraction, muscle atrophy or traumatic muscle injury can alter the type and relative abundance of particular factors released from muscle cells. The molecular and cellular pathways by which muscle-derived factors affect different types of bone cells (for example, osteoblasts, osteoclasts and osteocytes) are, however, poorly understood. Nevertheless, these findings further underscore the complex nature of muscle-bone interactions, and highlight the importance of integrating muscle biology and physiology into our understanding of bone growth, development and aging.