Bone and Muscle Endocrine Functions: Unexpected Paradigms of Inter-organ Communication

Abstract

Most physiological functions originate with the communication between organs. Mouse genetics has revived this holistic view of physiology through the identification of inter-organ communications that are unanticipated, functionally important, and would have been difficult to uncover otherwise. This Review highlights this point by showing how two tissues usually not seen as endocrine ones, bone and striated muscles, influence several physiological processes in a significant manner.

Figure 1. Endocrine Roles for Osteocalcin

Schematic representation of the main organs whose functions are affected by osteocalcin (pancreas and testes) and FGF23 (kidney), the two osteoblast-derived hormones. Gprc6a is the receptor for osteocalcin in pancreatic β-cells and Leydig cells of the testes; FGFR1 and Klotho mediates FGF23 signal in tubular cells of the kidney.

Figure 2. Functions of osteocalcin in the brain

Maternally derived osteocalcin crosses the placenta, reaches the developing brain and favors hippocampal development. In adult animals osteocalcin crosses the blood brain barrier regulates the synthesis of various neurotransmitters, prevents anxiety and favors spatial learning and memory. The receptor for osteocalcin in the brain has not been identified yet.

Figure 3. Endocrine signaling from striated muscles to distal tissues

Myostatin and IL-6 signal from skeletal muscle to distal tissues and also exert autocrine functions to suppress muscle growth and enhance glucose uptake, respectively. Natriuretic peptides (NPs) released from the heart regulate diverse processes in distal tissues. The Mediator subunit MED13 acts in the heart to enhance fatty acid oxidation in liver and white adipose tissue. The factor(s) that mediate(s) signaling from cardiac MED13 to distal tissues have not been identified.