Molecular bases of the crosstalk between bone and muscle.

Exercise is an evolutionary conserved survival function that nowadays has beneficial health effects. The increased metabolic activity of contracting skeletal muscle affects the biology of many organs involved in regulating muscle functions. The discovery of hormones and cytokines secreted by bone and skeletal muscle during exercise, has recently added experimental credence to the notion that a crosstalk exists between these organs. Bone through the hormone osteocalcin, promotes exercise capacity in the mouse. After binding to a G-coupled protein receptor, Gprc6a, osteocalcin increases nutrients uptake and catabolism in myofibers during exercise. The catabolic aspect of osteocalcin distinguishes it from insulin signaling. In addition, osteocalcin regulates the endocrine function of skeletal muscle because it enhances the expression of interleukin-6 (IL-6). IL-6 is produced and secreted by contracting skeletal muscle and exerts autocrine, paracrine and systemic effects. One of the systemic functions of IL-6 is to drive the generation of bioactive osteocalcin. Altogether, these studies have revealed a feed-forward loop between bone and skeletal muscle that are necessary and sufficient for optimum exercise capacity. This endocrine regulation of exercise biology, suggest novel and adapted strategies for the prevention or treatment of age related muscle loss.