Matrix Gla protein (MGP) and bone morphogenetic protein-2 in aortic calcified lesions of aging rats.
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 gamma-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-gamma-carboxylation of MGP, allowing unopposed BMP-2 activity.
Sweatt
A
A
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Sane
D C
DC
Hutson
S M
SM
Wallin
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001018:Aortic Diseases / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002114:Calcinosis / Q000378:metabolism*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D016326:Extracellular Matrix Proteins; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D013006:Growth Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009300:Nasal Septum / Q000002:abnormalities; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014812:Vitamin K / Q000494:pharmacology; D000097568:Matrix Gla Protein
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002118:Calcium; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D013006:Growth Hormone; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014812:Vitamin K; D000097568:Matrix Gla Protein; C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; C499469:recombinant human bone morphogenetic protein-2