Matrix Gla protein (MGP) and bone morphogenetic protein‐2 in aortic calcified lesions of aging rats

Summary.  The vitamin K‐dependent protein, matrix Gla protein (MGP) is a binding protein for bone morphogenetic protein‐2 (BMP‐2). Here we present additional evidence that the Ca2+‐induced conformer of the vitamin K‐dependent Gla region in MGP is involved in BMP‐2 binding. Recombinant BMP‐2 binds to the Gla‐containing region of MGP in the presence of Ca2+. Immunohistochemistry showed that calcified lesions in the aortic wall of aging rats contained elevated concentrations of MGP that was poorly γ‐carboxylated and did not bind BMP‐2. In contrast, we were able to identify glandular structures in the mucosa of the rat nasal septum that gave bright fluorescent signals with both antigens; confocal microscopy confirmed their colocalization. These results demonstrate that the BMP‐2/MGP complex exists in vivo, consistent with a role for MGP as a BMP‐2 inhibitor. Age‐related arterial calcification may be a consequence of under‐γ‐carboxylation of MGP, allowing unopposed BMP‐2 activity.