Mutual Modulation of Femarelle and Vitamin D Analog Activities in Human Derived Female Cultured Osteoblasts

Presentation Number: SAT 349
Date of Presentation: April 1st, 2017

Dalia Somjen*1, Sara Katzburg2, Orli Sharon1, David Hendel3, Gary H Posner4 and Naftali Stern5
1Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel, 2Tel aviv med ctr, Tel-aviv, Israel, 3Sharei Zedek medical center, 4The John Hopkins Univ, Baltimore, MD, 5Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel


Femarelle (F), a chemical derivative of the phytoestrogen daidzein (D), has an estrogen-like activity and activates human derived cultured female bone cells (hObs) which express receptors for estradiol-17β (E2; ERα and ERβ) and vitamin D (VDR). Estrogens and Vitamin D metabolites and analogs regulate cell proliferation (DNA) and energy metabolism through modulation of the specific activity of creatine kinase (CK). Pre- treatment with vitamin D less-calcemic analog: JKF 1624F2-2 (JKF) up-regulated responsiveness to E2 and to different estrogens via modulation of ERs mRNA expression. Estrogens, in turn, induce VDR and 25- hydroxy vitamin D3 1- α hydroxylase (1OHase) expression and 1,25(OH)2D3 (1,25D) synthesis. Here we compare the effects of F to those of D and E2 on DNA and CK, and examine whether or not these effects can be modulated by pre-treatment with the vitamin D analog JKF. We found: 1. F, D and E2 stimulated DNA [170% and 160% in pre and in post hObs respectively by F; 175% and160% respectively by D and 156% and150% respectively by E2] and CK [160 and 150% by F; 160 and 150% by D and 160 and 140% by E2 respectively]. The effect of F was not related to the age of patients from whom the cells were harvested. 2. JKF increased ERα (120 and 170% respectively) and decreased ERβ (45 and 40% respectively) mRNA expression, up-regulated DNA and CK response to E2 and D but not to F. 3. JKF increased only E2 but not D or F intracellular competitive binding in pre-menopausal, but not in post-menopausal hObs. 4. F, D and E2 increased VDR (145 and 130% by F; 130 and 125% by D and 150 and 140% by E2 respectively) and 1OHase mRNA expression (300 and 180% by F; 250 and 160% by D and 220 and 150% by E2 respectively) and its activity measured by 1,25D production (210 and 170% by F; 270 and 220% by D and 170 and 150% by E2 respectively), with slightly bigger effect in pre- compared to post- menopausal cells. In conclusion, F, D and E2 increase DNA and CK, 1,25D production as well as the mRNA expression of ERs, VDR and 1OHase. Pre- treatment with JKF modulates the effect of E2 and D but not of F. On the other hand all estrogens modulate VDR expression and both mRNA expression and activity of 1OHase in the cells which, in turn, up-regulate ERs expression and activity in hObs. The observation that the effects of F are independent of pre-treatment with vitamin D analog in women-derived hObs may offer an advantage in its use in post-menopausal women, since it appears to operated well even in the absence of vitamin D analog.


Nothing to Disclose: DS, SK, OS, DH, GHP, NS