Smooth muscle cells deficient in osteopontin have enhanced susceptibility to calcification in vitro.

Abstract

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 alpha-actin and SM22alpha. 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.

• Authors: Mei Y Speer, Yung-Ching Chien, Mary Quan, Hsueh-Ying Yang, Hojatollah Vali, Marc D McKee, Cecilia M Giachelli
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 66 Issue 2 Pg. 324-33 (May 01 2005) ISSN: 0008-6363 [Print] England
• PMID: 15820201 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Complementary
• Phosphates
• SPP1 protein, human
• Sialoglycoproteins
• Spp1 protein, mouse
• Osteopontin

Topics

• Animals
• Aorta
• Calcinosis (etiology, metabolism)
• Cell Culture Techniques
• DNA, Complementary (administration & dosage)
• Disease Susceptibility
• Genetic Vectors (administration & dosage)
• Mice
• Mice, Knockout
• Muscle, Smooth, Vascular (metabolism)
• Osteopontin
• Phosphates (pharmacology)
• Retroviridae (genetics)
• Sialoglycoproteins (deficiency, genetics)
• Transduction, Genetic (methods)