Effects of genistein on expression of bone markers during MC3T3-E1 osteoblastic cell differentiation.
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.
Chen
Xiaowei
X
Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Garner
Sanford C
SC
Quarles
L Darryl
LD
Anderson
John J B
JJ
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
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