Osteocalcin synthesis in osteoblasts. The BGLAP gene encoding osteocalcin is mainly expressed in osteoblasts and to lesser extent odontoblasts. After transcription (which is stimulated by vitamin D) the preproosteocalcin peptide undergoes proteolysis giving rise to a prepeptide (23 aa) and a proosteocalcin peptide (75 aa). The latter 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 pro-osteocalcin. Then Gla and Glu pro-osteocalcin peptides are subjected to a final proteolytic process that produces, respectively, carboxylated and undercarboxylated osteocalcins. Both forms are released from osteoblasts in a process which is calciumdependent. While the carboxylated Glaresidues are involved in calcium and hydroxyapatite binding, allowing osteocalcin deposition on mineralized bone matrix, undercarboxylated osteocalcin has a low affinity for hydroxyapatite and is more easily released into the circulation.