Femarelle (F) activates human derived cultured female bone cells (hObs) and human bone cell line
(SaOS2), which express receptors for estradiol-17β (E2; ERα and ERβ) and vitamin D (VDR). Vitamin D metabolites
and analogs regulate cell proliferation (DNA) and the specific activity of creatine kinase (CK). Pretreatment
with vitamin D less-calcemic analog: JKF 1624F2-2 (JKF) up-regulated responsiveness to estrogens
via modulation of ERs mRNA expression. The estrogens in turn induce VDR and 25- hydroxy vitamin D3 1-α hydroxylase (1OHase) expression and 1,25(OH)2D3 (1,25D) synthesis. We compared the effects of F to
those of its precourser daidzein (D) and E2 on DNA and CK, and effect of JKF pretreatment. We found: 1. F,
D and E2 stimulated DNA and CK. 2. JKF increased ERα and decreased ERβ mRNA expression, up-regulated
DNA and CK response to E2 and D but not to F. 3. JKF increased only E2 intracellular competitive binding. 4.
F, D and E2 increased VDR and 1OHase mRNA expression and its activity measured by 1,25D production. In
conclusion, F, D and E2 increases DNA and CK, as well as 1,25D production and VDR and 1OHase mRNA
expression. Pre- treatment with JKF modulates the effect of E2 and D but not of F while all estrogens modulate
VDR expression and both mRNA expression and activity of 1OHase in the cells. These finding that F effects
are not affected by the vitamin D levels in female-derived osteoblasts may contribute to its beneficial
role in treatment of post-menopausal bone loss.
Keywords: Osteoblasts, vitamin D, estrogens, DNA, CK, VDR, ERs, 10 Hase.
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