title: Effects of genistein on expression of bone markers during MC3T3-E1 osteoblastic cell differentiation.
abstract: In this in vitro study, the hypothesis that the beneficial effects of dietary genistein on bone are through the modulation of the bone marker synthesis by osteoblastic MC3T3-E1 cells was tested, and the possible roles of estrogen receptors in the actions of genistein on osteoblastic cells were also examined. Interleukin-6 production was decreased 40% to 60% in osteoblastic cells treated with genistein from either day 8-16 or day 12-16, at dietarily achievable concentrations (10(-10) to 10(-8) M) (P<0.05). The mRNA expression of osteoprotegerin increased about 140% in cells treated from with genistein day 4-8 at a concentration of 10(-8) M (P<0.05). The ratio of estrogen receptor-alpha to beta expression increased 10-fold from day 0 to 12 of culture (P<0.05). Correlating with this time-dependent variation in estrogen receptor expression, treatments of 17beta-estradiol and genistein had opposite dose patterns on the ratio of estrogen receptor-alpha to beta expression following treatment from day 4 to 6 compared to from day 0 to 2. The addition of ICI-182,780, an estrogen receptor blocker, reduced the inhibitory effect of genistein on IL-6 production by 30-50%. In summary, these findings suggest that the beneficial skeletal effects of genistein, at dietarily achievable levels, appear to be mediated, at least in part, by interleukin-6 and osteoprotegerin, and estrogen receptors play important roles in the inhibition of interleukin-6 synthesis by genistein in osteoblastic MC3T3-E1 cells.
authors.affiliation: Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.forename: Sanford C
authors.initials: SC
authors.lastname: Garner
authors.forename: L Darryl
authors.initials: LD
authors.lastname: Quarles
authors.forename: John J B
authors.initials: JJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D015850:Interleukin-6 / Q000032:analysis; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D010006:Osteoblasts / Q000737:chemistry / Q000166:cytology*; D053244:Osteoprotegerin; D010641:Phenotype; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006023:Glycoproteins; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D004958:Estradiol; D019833:Genistein; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases