The skeleton as an endocrine organ: metabolic functions of osteocalcin

Abstract

The skeleton is one of the biggest systems in a vertebrate animal and, as such, it is reasonable to speculate that it cannot function isolated from the rest of the organism. In fact,
we know that complex systems exist for the cross-regulation between the skeleton and several other organs. Today, we have the tools that allow us to perform genetic suppression
in specific cells or tissues. This has allow us understand the mechanisms by which the organs communicate with each other and has revitalized the concept of organismal physiology as a whole.
Studies conducted in recent years have uncovered unexpected functions performed by the skeleton. One of these is the control of global energy metabolism, through the secretion of osteocalcin, a protein produced by osteoblasts that acts as a hormone regulating insulin secretion, insulin sensitivity and energy expenditure. The evidence comes from the analysis of mice lacking insulin receptor (InsR) exclusively in osteoblasts. These mice have a global metabolic phenotype demonstrating that the action of insulin in osteoblasts promotes the homeostasis of glucose throughout the body. This action of insulin in osteoblasts is mediated by the negative regulation of the carboxylation (and bioavailability) of osteocalcin. The decarboxylation (and activation) of osteocalcin, in turn, occurs in the osteoclastic resorption pit. Briefly: the osteoblast is a target used by insulin to control the homeostasis of glucose throughout the body and bone resorption is the mechanism that regulates the activation of osteocalcin.