JCB logo
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 7 June 2004. doi:10.1083/jcb.200402046
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 165, Number 5, 625-630
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2143K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Murshed, M.
Right arrow Articles by Karsenty, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Murshed, M.
Right arrow Articles by Karsenty, G.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Report

Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins



Monzur Murshed1,2, Thorsten Schinke1, Marc D. McKee3,4, and Gerard Karsenty1,2

1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030
2 Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030
3 Faculty of Dentistry, McGill University, Montreal, Quebec, Canada H3A 2B2
4 Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada H3A 2B2

Address correspondence to Gerard Karsenty, Baylor College of Medicine, One Baylor Plaza, Rm. S921, Houston, TX 77030. Tel.: (713) 798-5489. Fax: (713) 798-1530. email: karsenty{at}bcm.tmc.edu

Extracellular matrix mineralization (ECMM) is a physiologic process in the skeleton and in teeth and a pathologic one in other organs. The molecular mechanisms controlling ECMM are poorly understood. Inactivation of Matrix gla protein (Mgp) revealed that MGP is an inhibitor of ECMM. The fact that MGP is present in the general circulation raises the question of whether ECMM is regulated locally and/or systemically. Here, we show that restoration of Mgp expression in arteries rescues the arterial mineralization phenotype of Mgp–/– mice, whereas its expression in osteoblasts prevents bone mineralization. In contrast, raising the serum level of MGP does not affect mineralization of any ECM. In vivo mutagenesis experiments show that the anti-ECMM function of MGP requires four amino acids which are {gamma}-carboxylated (gla residues). Surprisingly, another gla protein specific to bone and teeth (osteocalcin) does not display the anti-ECMM function of MGP. These results indicate that ECMM is regulated locally in animals and uncover a striking disparity of function between proteins sharing identical structural motifs.

Key Words: MGP; osteocalcin; ECM; mineralization; local regulation

Abbreviations used in this paper: ECMM, ECM mineralization; MGP, matrix gla protein; VSMC, vascular smooth muscle cell; WT, wild-type.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related Article

Mineralized mice
Aparna Sreenivasan
J. Cell Biol. 2004 165: 602-603. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents