Mutual modulation of femarelle and vitamin D analog activities in human derived female cultured osteoblasts. Issue 1 (1st January 2017)

• Record Type: Journal Article
• Authors: Somjen, D.; Katzburg, S.; Sharon, O.; Knoll, E.; Hendel, D.; Posner, G.H.
• Editors: Winder, Steve
• Is Part Of: Cogent biology. Volume 3:Issue 1(2017)
• Publication Date: 2017-01-01
• Subjects: human osteoblasts -- femarelle -- DNA -- CK -- phytoestrogens -- JKF -- ER -- VDR; Biology -- Periodicals; Biology; Periodicals; 570.5
• DOI: 10.1080/23312025.2017.1374919
• Languages: English
• ISSNs: 2331-2025

Abstract

Abstract: Introduction: Pre-, post-menopausal, and male human osteoblasts (hObs) express estradiol-17β (E2 ) receptors α and β (ERα, ERβ), vitamin D receptor (VDR), and 25-hydroxy vitamin D3 1-α hydroxylase (1OHase) and produce 1, 25 (OH)2 D3 (1, 25D). Pre-treatment with JKF (JKF 1624F2–2 ) up-regulated estrogenic responsiveness, via modulation of ERs expression and E2 binding. These estrogens induce VDR and 1OHase expression and 1, 25D production. Purpose: Compared the effects of femarelle (F) to daidzein (D) and E2 by themselves and their modulation by JKF. Methods: hObs derived from human bones at different ages and sex were cultured, treated with different hormones and analyzed for the different parameters. Results: (1) F, D and E2 stimulated 3 [H] thymidine incorporation (DNA) and creatine kinase specific activity (CK) in female but not in male hObs. The responses to E2 and to D unlike to F were up-regulated by JKF. (2) All hormones increased ERα and decreased ERβ mRNA in all hObs. (3) JKF modulated in different ways the expressions of ERα and ERβ mRNA in all hObs. (4) JKF did not significantly modulate the expressions of ERα and ERβ mRNA in all hObs. (5) JKF increased intracellular competitive binding of E2 by all hormones only in female hObs. (6) Pre-treatment with all hormones increased VDR and 1OHase expression and 1, 25D formation in pre- and post-, but only JKF modulated it in male hObs. Conclusions: F, D and E2 increase different parameters in hObs. However, pre-treatment with JKF modulates the effect of E2 and D but not of F. F reciprocally modulates mRNA expression and activity of 1OHase which in turn up-regulate ERs expression and activity. These finding may contribute to F's beneficial role in treatment of post-menopausal bone loss even in vitamin D deficiency.