Review Article

Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

Figure 2

OCN is synthesized in osteoblasts. OCN is mainly expressed in osteoblasts. After transcription, which is stimulated by Vitamin D, the prepro-OCN peptide will be proteolysed and forms a prepeptide (23 aa) and a pro-OCN peptide (75 aa). The pro-OCN peptide can be carboxylated at Glu residues 17, 21, and 24, resulting in formation of Gla residues in a Vitamin K dependent process. Generally, this process only occurs in a proportion of newly synthesized proosteocalcin. Then Gla and Glu pro-OCN peptides are subjected to a final proteolytic process that produces cOCN and ucOCN. Both forms are released from osteoblasts in a process which is calcium dependent. While the carboxylated Gla residues are involved in calcium and hydroxyapatite binding, allowing OCN deposition on mineralized bone matrix, ucOCN has a low affinity for hydroxyapatite and is more easily released into the circulation. OCN, osteocalcin; ucOCN, uncarboxylated osteocalcin; VDR, Vitamin D receptor; VDRE, Vitamin D receptor element.