Differential effects of 17β-estradiol and raloxifene on VSMC phenotype and expression of osteoblast-associated proteins

Ewa Rzewuska-Lech, Muthuvel Jayachandran, Lorraine A. Fitzpatrick, Virginia M. Miller

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Several studies demonstrate an association between osteoporosis and arterial calcific disease, both of which being common in elderly women. Estradiol and raloxifene, a selective estrogen receptor modulator, prevent bone loss in postmenopausal women. Little is known regarding how these agents affect arterial calcification. The aim of this study was to determine whether or not 17β-estradiol and raloxifene reduced vascular smooth muscle cell (VSMC) differentiation and expression of bone-associated proteins during phosphate-induced calcification in vitro. Aortic VSMC were cultured from adult, gonadally intact, and ovariectomized (OVX) female pigs. Calcifying medium was added, and cells were treated with solvent (control), 17β-estradiol (E 2), or raloxifene. Extent of calcification and phenotypic expression of bone-associated proteins [matrix gla protein (MGP), osteoprotegerin (OPG), and bone sialoprotein (BSP)] were examined at 3-day intervals over 2 wk. Calcium content increased in all groups but was greater in VSMC derived from intact compared with OVX animals. E2 reduced calcification and preserved a contractile phenotype. Expression of OPG significantly decreased with time; this decrease was significantly greater in VSMC derived from OVX compared with gonadally intact pigs. E2 and raloxifene preserved expression of OPG only in VSMC from intact pigs. Expression of MGP increased significantly with time and was not affected by E2 or raloxifene treatments. E 2 treatment significantly inhibited synthesis of BSP in cells from both groups. In conclusion, E2 slows differentiation of VSMC induced by excess phosphate. Effectiveness of raloxifene to preserve expression of bone cell-associated proteins depends on the hormonal status of the tissue donor.

Original languageEnglish (US)
Pages (from-to)E105-E112
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number1 52-1
StatePublished - Jul 2005


  • Estrogen
  • Raloxifene
  • Selective receptor modulator
  • Smooth muscle phenotype
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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