VITAMIN K-DEPENDENT CALCIUM BINDING PROTEINS OF THE EXTRACELLULAR BONE MATRIX

Abstract

This chapter discusses the structure and the possible functions of vitamin K-dependent bone proteins. Bone Gla Protein (BGP) was the first noncollagenous bone protein to be sequenced, and Matrix Gla Protein (MGP) is the second. The role of Gla residues in BGP has been explored by comparing the properties of native BGP with BGP in which the Gla residues have been thermally decarboxylated to Glu residues by a highly specific chemical modification. BGP is also the first noncollagenous bone protein for which a complete cDNA structure has been established. BGP was named as such because it is a Gla-containing protein associated with the mineral component of bone. MGP was so named because a substantial fraction of MGP in bone does not emerge during demineraiization but emerges only on the subsequent extraction of the demineralized matrix with denaturants, such as guanidine HCl and urea. Developmental studies indicate that MGP and BGP may be expressed at different stages in the calcification of bone. The main evidence on the function of vitamin K-dependent proteins in bone and cartilage metabolism has come from the analysis of rats treated with the vitamin K-antagonist Warfarin.