Modulation of the binding of matrix Gla protein (MGP) to bone morphogenetic protein-2 (BMP-2)

Matrix cia protein (MGP) is an inhibitor of calcification of the arterial w all but the mechanism of inhibition has not been resolved. Since chondrogen esis has been identified in calcified arteries from MPG null mice, we hypot hesized that locally produced MGP might inhibit calcification by neutralizi ng the known effect of bone morphogenetic proteins (BMPs) as promoters of c hondrogenesis and bone formation. As the first step to test this hypothesis , we demonstrate that MGP is a binding protein for I-125-BMP-2. Optimal bin ding is dependent on metals which suggests that the metal binding Gla regio n in MGP is involved. MGP is shown to undergo a Ca++ induced conformational change despite the presence of the gamma -carboxylase binding site being p art of the mature protein sequence. The data propose that MGP matures earli er in the secretory pathway than other vitamin K-dependent proteins. Antibo dies were used in an attempt to identify MGP in bovine serum. Conformationa l specific MGP antibodies were shown to also recognize the Gla region in pr othrombin and factor X but did not identify MGP in serum. This finding is s upported by electrophoresis data which demonstrate the absence of MGP among Ba-citrate absorbed vitamin K-dependent serum proteins. We conclude that M GP does not exist in normal bovine serum.