TGF-beta 1 and 25-hydroxycholesterol stimulate osteoblast-like vascular cells to calcify

J Clin Invest. 1994 May;93(5):2106-13. doi: 10.1172/JCI117205.

Abstract

Previous studies in our laboratory demonstrated messenger RNA for bone morphogenetic protein-2a in human calcified plaque, suggesting that arterial calcification is a regulated process, similar to osteogenesis. To further test this hypothesis, we have isolated and cloned a subpopulation of cells from bovine aortic media that show osteoblastic potential. These novel cells are primarily distinguished from smooth muscle cells by expression of a surface marker preliminarily identified as a modified form of the ganglioside sialyl-lactosylceramide (GM3). Osteoblastic potential was indicated by high levels of alkaline phosphatase and collagen I, expression of osteopontin and osteonectin (SPARC), and production of bone-specific osteocalcin and hydroxyapatite. Cultures of these cells were stimulated to form increased numbers of calcium-mineral-producing nodules by the oxysterol 25-hydroxycholesterol as well as by transforming growth factor-beta 1, both known to be present in atherosclerotic lesions. The stimulation of calcifying vascular cells in the artery wall by these two factors suggests a possible mechanism for the colocalization of calcification with atherosclerosis in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaline Phosphatase / isolation & purification
  • Animals
  • Aorta / cytology
  • Aorta / drug effects*
  • Aorta / pathology
  • Arteriosclerosis / etiology
  • Biomarkers
  • Calcinosis / chemically induced*
  • Cattle
  • Clone Cells
  • Cytokines / pharmacology
  • G(M3) Ganglioside / isolation & purification
  • Histocytochemistry
  • Humans
  • Hydroxycholesterols / pharmacology*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteocalcin / isolation & purification
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Biomarkers
  • Cytokines
  • G(M3) Ganglioside
  • Hydroxycholesterols
  • Transforming Growth Factor beta
  • Osteocalcin
  • 25-hydroxycholesterol
  • Alkaline Phosphatase