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Mineralized mice

Mineralization (red) of the aorta is prevented by local (left), but not global (right), Mgp expression.

Lot's wife turned into a pillar of salt because she looked back at Sodom and Gomorrah; but most people are saved from being turned into one big pile of minerals by mineralization inhibitors. Murshed et al. (page 625) now show that these inhibitors act locally and selectively despite circulating systemically. A better understanding of how this works could suggest ways to tackle the ectopic mineralization seen during arthritis.

Mineralization is necessary in bone, but must be prevented in soft tissues—such as artery walls and cartilage—that have an extensive, mineralization-prone extracellular matrix (ECM). It is unclear how this distinction is made by inhibitors that are made locally but also circulate systemically.

Murshed et al. investigated this process by expressing a known mineralization inhibitor, Matrix gla protein (MGP), in various mouse tissues. MGP could act locally when expressed locally: expression in arterial walls inhibited the ectopic mineralization normally seen there in mice lacking MGP; and expression in bone-generating osteoblasts reduced bone mineralization in wild-type mice. But MGP expressed in liver, so that it reached high levels in the bloodstream, did not have such effects. Although the resulting serum could inhibit osteoblast mineralization in vitro, there was no effect on either ectopic arterial wall mineralization or normal bone mineralization.

The authors confirmed that the mineral-binding gla (-carboxylated glutamic acid) residues of MGP are necessary for its inhibitor activity; the bone protein osteocalcin has similar gla residues but was found not to be a mineralization inhibitor. But the mechanism that keeps MGP action local remains to be determined.

Aparna Sreenivasan

aparnas{at}nasw.org

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Related Article

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

Monzur Murshed, Thorsten Schinke, Marc D. McKee, and Gerard Karsenty
J. Cell Biol. 2004 165: 625-630. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 669K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sreenivasan, A. Search for Related Content PubMed Articles by Sreenivasan, A. Related Collections Related Article Social Bookmarking                            What's this?