Smooth muscle cell phenotypic transition associated with calcification

Upregulation of Cbfa1 and downregulation of smooth muscle lineage markers

Susie A. Steitz, Mei Y. Speer, Gabrielle Curinga, Hsueh Ying Yang, Paul Haynes, Ruedi Aebersold, Thorsten Schinke, Gerard Karsenty, Cecilia M. Giachelli*

*Corresponding author for this work

Research output: Contribution to journalArticle

598 Citations (Scopus)

Abstract

Bovine aortic smooth muscle cell (BASMC) cultures undergo mineralization on addition of the organic phosphate donor, β-glycerophosphate (βGP). Mineralization is characterized by apatite deposition on collagen fibrils and the presence of matrix vesicles, as has been described in calcified vascular lesions in vivo as well as in bone and teeth. In the present study, we used this model to investigate the molecular mechanisms driving vascular calcification. We found that BASMCs lost their lineage markers, SM22α and smooth muscle α-actin, within 10 days of being placed under calcifying conditions. Conversely, the cells gained an osteogenic phenotype as indicated by an increase in expression and DNA-binding activity of the transcription factor, core binding factor α1 (Cbfal). Moreover, genes containing the Cbfal binding site, OSE2, including osteopontin, osteocalcin, and alkaline phosphatase were elevated. The relevance of these in vitro findings to vascular calcification in vivo was further studied in matrix GLA protein null (MGP-/-) mice whose arteries spontaneously calcify. We found that arterial calcification was associated with a similar loss in smooth muscle markers and a gain of osteopontin and Cbfal expression. These data demonstrate a novel association of vascular calcification with smooth muscle cell phenotypic transition, in which several osteogenic proteins including osteopontin, osteocalcin, and the bone determining factor Cbfal are gained. The findings suggest a positive role for SMCs in promoting vascular calcification.

Original languageEnglish
Pages (from-to)1147-1154
Number of pages8
JournalCirculation Research
Volume89
Issue number12
Publication statusPublished - 7 Dec 2001
Externally publishedYes

Keywords

  • Core binding factor α1
  • Phenotype
  • Smooth muscle cells
  • Vascular calcification

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    Steitz, S. A., Speer, M. Y., Curinga, G., Yang, H. Y., Haynes, P., Aebersold, R., ... Giachelli, C. M. (2001). Smooth muscle cell phenotypic transition associated with calcification: Upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circulation Research, 89(12), 1147-1154.