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

J Thromb Haemost. 2003 Jan;1(1):178-85. doi: 10.1046/j.1538-7836.2003.00023.x.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aortic Diseases / metabolism*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / antagonists & inhibitors
  • Bone Morphogenetic Proteins / chemistry
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Calcinosis / metabolism*
  • Calcium / chemistry
  • Calcium / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Calcium-Binding Proteins / pharmacology
  • Cattle
  • Extracellular Matrix Proteins*
  • Female
  • Fluorescent Antibody Technique / methods
  • Growth Hormone / chemistry
  • Growth Hormone / genetics
  • Growth Hormone / metabolism
  • Humans
  • Immunohistochemistry
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / pathology
  • Nasal Mucosa / ultrastructure
  • Nasal Septum / abnormalities
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Transforming Growth Factor beta*
  • Vitamin K / pharmacology

Substances

  • BMP2 protein, human
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • matrix Gla protein
  • recombinant human bone morphogenetic protein-2
  • Vitamin K
  • Growth Hormone
  • Calcium