Osteocalcin promotes bone mineralization but is not a hormone
Stavros C. Manolagas
Abstract
During the last 24 years the bone and mineral metabolism research community (and the National Institutes of Health and numerous other national and international funding agencies that support it) have devoted a great deal of intellectual energy and resources to some provocative, sometimes controversial, ideas about osteocalcin (OCN). OCN is a 46 amino-acid protein that is produced and secreted almost exclusively by osteoblasts, terminally differentiated cells responsible for the synthesis and mineralization of bone matrix during development of the skeleton and its periodic regeneration throughout life. Osteoblasts originate from mesenchymal progenitors and are short-lived cells that are constantly replaced, depending on the demand for bone formation in a particular location and time OCN secreted by osteoblasts contains three -carboxyglutamic acid residues that confer high affinity to the bone hydroxyapatite matrix. However, when bone is resorbed by osteoclasts, a macrophage-derived cell type, the acidic pH in the resorption compartment causes the carboxyl groups on OCN to be removed, and decarboxylated OCN is released into circulation. The circulating levels of decarboxylated OCN are, therefore, dependent on the rate of bone turnover, also known as remodeling.