Developmental appearance of the vitamin K-dependent protein of bone during calcification. Analysis of mineralizing tissues in human, calf, and rat.

Several mineralizing tissues have been analyzed for the vitamin K-dependent protein of bone (BGP) in order to establish the temporal relationship between initial mineral deposition and the appearance of BGP. These studies demonstrate that the appearance of BGP in developing bone is not dependent on birth, as had been suggested in earlier studies of rat development, but rather on the prior deposition of bone mineral. In fetal human bone, the level of BGP (grams of BGP/mol of bone PO4) rises from 5% of the adult level at 10 weeks gestational age to the adult level at 15 weeks. Thus, adult levels of BGP are reached in human bone shortly after the initial appearance of mineral and long before birth. In adolescent rats, which have overall levels of BGP in bone near the adult level, the appearance of BGP at the ends of growing bones and in bone induced by implantation of demineralized bone matrix follows mineral deposition by approximately 2 weeks. The relative absence of BGP in initially deposited bone mineral and its subsequent appearance several days later may be causally related to the maturation of bone mineral to hydroxyapatite, a structure which binds BGP. The implications of the timing of BGP appearance in mineralizing tissues to its possible function in bone are discussed.