Isoflavones regulate interleukin-6 and osteoprotegerin synthesis during osteoblast cell differentiation via an estrogen-receptor-dependent pathway.
The hypothesis tested in this in vitro study was that the expression and production of dietary isoflavone-mediated osteoclastogenesis-regulatory cytokines, such as interleukin-6 (IL-6) and osteoprotegerin (OPG), are related to the different levels of estrogen receptors expressed in two hFOB osteoblastic cell lines. OPG mRNA expression was significantly increased in both hFOB1.19 and hFOB/ER9 cells treated with 17 beta-estradiol, genistein, or daidzein at 10(-8)M in comparison to vehicle (control) (P<0.05). In both cell lines, the release of IL-6 was suppressed, while OPG production was enhanced by isoflavone treatments (P<0.05). The increased expression of OPG and decreased IL-6 production by isoflavones were dose-dependent. Responses to isoflavones were much stronger in hFOB/ER9 cells, which express the estrogen receptor 20 times higher than those in hFOB1.19 cells. After adding the ER binding blocker, ICI-182,780, the effects of isoflavones on OPG and IL-6 production disappeared. In summary, the inhibition by dietary isoflavones of IL-6 production and the stimulation of OPG appear to be mediated, at least in part, via a genomic pathway operating through estrogen receptors and gene expression mechanisms.
Chen
X W
XW
Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill, NC 27599-7400, USA.
Garner
S C
SC
Anderson
J J B
JJ
D002454:Cell Differentiation; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007529:Isoflavones / Q000494:pharmacology*; D053244:Osteoprotegerin; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor
D006023:Glycoproteins; D015850:Interleukin-6; D007529:Isoflavones; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human