Document Detail


Osteopontin upregulation and polymerization by transglutaminase 2 in calcified arteries of Matrix Gla protein-deficient mice.
MedLine Citation:
PMID:  17189522     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Matrix Gla protein (MGP) is a potent inhibitor of soft tissue calcification, and Mgp gene deletion in mice results in arterial calcification. Our aim was to examine osteopontin (OPN) expression and localization, and posttranslational processing of OPN by the crosslinking enzyme transglutaminase 2 (TG2), in the calcified aorta of Mgp-deficient (Mgp(-/-)) mice. Using immunohistochemistry and light and electron microscopy, we report that following mineralization occurring in the arterial media of Mgp(-/-) aortas, OPN is upregulated and accumulates at the surface of the calcified elastic lamellae. Macrophages were observed in direct contact with this OPN-rich layer. Western blot analysis of extracted Mgp(-/-) aortas revealed that the majority of the OPN was in high molecular mass protein complexes, indicating modification by a crosslinking enzyme. Consistent with this observation, TG2 expression and gamma-glutamyl-epsilon-lysyl crosslink levels were also increased in Mgp(-/-) aortas. In addition to the mineral-inhibiting actions of OPN, and based on data linking OPN and TG2 with cell adhesion in various cell types including monocytes and macrophages, we propose that TG2 interactions with OPN lead to protein polymerization that facilitates macrophage adhesion to the calcified elastic lamellae to promote clearance of the ectopic mineral deposits.
Authors:
Mari T Kaartinen; Monzur Murshed; Gerard Karsenty; Marc D McKee
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-12-22
Journal Detail:
Title:  The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society     Volume:  55     ISSN:  0022-1554     ISO Abbreviation:  J. Histochem. Cytochem.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-19     Completed Date:  2007-05-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815334     Medline TA:  J Histochem Cytochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  375-86     Citation Subset:  IM    
Affiliation:
Faculty of Dentistry, McGill University, Strathcona Bldg. Room M-72, 3640 University Street, Montreal, QC, Canada H3A 2B2. mari.kaartinen@mcgill.ca
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Thoracic / metabolism*,  pathology,  ultrastructure
Blotting, Western
Calcinosis / metabolism*,  pathology
Calcium-Binding Proteins / deficiency*,  genetics
Extracellular Matrix Proteins / deficiency*,  genetics
Female
GTP-Binding Proteins / metabolism*
Immunohistochemistry
Macrophages / metabolism,  pathology
Male
Mice
Mice, Knockout
Microscopy, Electron
Osteopontin / metabolism*
Polymers / metabolism
Transglutaminases / metabolism*
Up-Regulation
Chemical
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Extracellular Matrix Proteins; 0/Polymers; 0/matrix Gla protein; 106441-73-0/Osteopontin; EC 2.3.2.-/transglutaminase 2; EC 2.3.2.13/Transglutaminases; EC 3.6.1.-/GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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