Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Aortic Diseases / metabolism*
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / antagonists & inhibitors
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Bone Morphogenetic Proteins / chemistry
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism*
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Calcinosis / metabolism*
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Calcium / chemistry
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Calcium / metabolism*
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Calcium-Binding Proteins / metabolism*
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Calcium-Binding Proteins / pharmacology
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Cattle
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Extracellular Matrix Proteins*
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Female
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Fluorescent Antibody Technique / methods
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Growth Hormone / chemistry
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Growth Hormone / genetics
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Growth Hormone / metabolism
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Humans
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Immunohistochemistry
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Matrix Gla Protein
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Microscopy, Confocal
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Molecular Sequence Data
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Nasal Mucosa / metabolism
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Nasal Mucosa / pathology
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Nasal Mucosa / ultrastructure
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Nasal Septum / abnormalities
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins
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Transforming Growth Factor beta*
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Vitamin K / pharmacology
Substances
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BMP2 protein, human
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Bmp2 protein, rat
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Calcium-Binding Proteins
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Extracellular Matrix Proteins
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Recombinant Proteins
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Transforming Growth Factor beta
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recombinant human bone morphogenetic protein-2
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Vitamin K
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Growth Hormone
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Calcium