Osteocalcin: the vitamin K-dependent Ca2+-binding protein of bone matrix

Abstract

Osteocalcin is an abundant Ca2+-binding protein indigenous to the organic matrix of bone, dentin, and possibly other mineralized tissues. This protein contains 47-50 amino acid residues (molecular weight 5,200-5,900) depending on the species. Osteocalcin is distinguished by its content of three gamma-carboxyglutamic (Gla) residues. The vitamin-K-dependent biosynthesis of osteocalcin occurs in bone, and the protein is not homologous to the Gla-containing regions of known vitamin-K-dependent blood coagulation proteins. The two major structural features of osteocalcin which appear to control its function include: the 'Gla helix', a compact Ca2+-dependent alpha-helical conformation, in which the three Gla residues are aligned to facilitate adsorption to hydroxyapatite, and the 'COOH-terminal beta-sheet' which exhibits chemoattractant activity toward mononuclear leukocytes, specifically monocytes, the putative precursors of osteoclasts. While the biological function of osteocalcin is unknown, it appears to be a highly specific osteoblastic marker produced during bone formation, and is rapidly becoming a clinically important diagnostic parameter of bone pathology. This article reviews recent advances in the understanding of osteocalcin.