Copyright © 2005, European Society of Cardiology
Smooth muscle cells deficient in osteopontin have enhanced susceptibility to calcification in vitro
aBioengineering Department, Box 351720 University of Washington, Seattle, WA 98195, U.S.A.
bDepartment of Anatomy and Cell Biology, and Faculty of Dentistry, McGill University, Montreal, Quebec, Canada
* Corresponding author. Tel.: +1 206 543 0205; fax: +1 206 616 9763. Email address: Ceci{at}u.washington.edu
Objective: Vascular calcification is an actively regulated process, correlating with cardiovascular morbidity and mortality especially in patients with diabetes and chronic renal diseases. Osteopontin (OPN) is abundantly expressed in human calcified arteries and inhibits vascular calcification in vitro and in vivo. How OPN functions in vascular calcification, however, is less clear.
Methods: Smooth muscle cells (SMCs) were isolated from aortas of OPN knock-out (OPN–/–) and wild type (OPN+/+) mice.
Results: OPN–/– SMCs were identical to OPN+/+ SMCs in morphology and stained positively for SM lineage proteins, desmin, smooth muscle 
-actin and SM22. No spontaneous calcification was observed in OPN–/– SMCs under normal culture conditions or in medium containing 1%, 3%, or 5% fetal bovine serum. However, when cultured in medium containing elevated concentrations of inorganic phosphate, an inducer of vascular calcification, a significantly higher calcification was observed in OPN–/– SMCs compared to OPN+/+ SMCs that, in response to elevated phosphate, synthesized and secreted OPN into the culture. Finally, retroviral transduction of mouse OPN cDNA into OPN–/– SMCs rescued the calcification phenotype of the cells.
Conclusion: These results are the first to demonstrate an inhibitory role of endogenously produced OPN on SMC calcification, suggesting a novel feedback mechanism where OPN produced locally by the SMCs may serve as an important inducible inhibitor of vascular calcification.
KEYWORDS Biomineralization; Bioapatite; Vascular calcification; Osteopontin; Smooth muscle cells
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