Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 161, Issue 6, Pages 2035-2046Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0002-9440(10)64482-3
Keywords
-
Categories
Funding
- NHLBI NIH HHS [1R01 HL 62329-01, R01 HL062329] Funding Source: Medline
- NIGMS NIH HHS [GM 07037, T32 GM007037] Funding Source: Medline
Ask authors/readers for more resources
Ectopic calcification, the abnormal calcification of soft tissues, can have severe clinical consequences especially when localized to vital organs such as heart valves, arteries, and kidneys. Recent observations suggest that ectopic calcification, like bone biomineralization, is an actively regulated process. These observations have led a search for molecular determinants of ectopic calcification. A candidate molecule is osteopontin (OPN), a secreted phosphoprotein invariantly associated with both normal and pathological mineral de posits. In the present study, OPN was found to he a natural inhibitor of ectopic calcification in vivo. Glutaraldehyde-fixed aortic valve leaflets showed accelerated and fourfold to fivefold greater calcification after subcutaneous implantation into OPN-null mice compared to wild-type mice. In vitro and in vivo studies suggest that OPN not only inhibits mineral deposition but also actively promotes its dissolution by physically blocking hydroxyapatite crystal growth and inducing expression of carbonic anhydrase H in monocytic cells and promoting acidification of the extracellular milieu. These findings suggest a novel mechanism of OPN action and potential therapeutic approach to the treatment of ectopic calcification.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available