金雀异黄素通过雌激素受体β增加人成骨细胞护骨素与破骨细胞分化因子表达比值

Genistein Increases the Ratios of OPG/RANKL Expression through ER-β in Human Osteoblast

目的探讨植物雌激素———金雀异黄素(genistein)对人成骨细胞(HOB)作用的分子机制。方法采用细胞培养结合Western blot方法,观察不同浓度金雀异黄素对HOB细胞的护骨素(OPG)、破骨细胞分化因子(RANKL)、雌激素受体(ER-,αER-β)蛋白质的影响。结果①中、大剂量金雀异黄素明显上调HOB细胞OPG蛋白质的表达、下调RANKL蛋白质的表达;雌激素受体拮抗剂ICI 182.780(10-8mol/L)拮抗金雀异黄素(10-8mol/L)的上述作用。②大剂量金雀异黄素刺激HOB细胞ER-β蛋白质的表达;各组ER-α蛋白质的表达量与对照组比较,差异无显著性意义(均P>0.05)。③OPG/RANKL比值与金雀异黄素剂量成正相关关系(r=0.694,P<0.05)。结论金雀异黄素通过ER-β上调HOB细胞OPG表达、下调RANKL表达,该雌激素样效应可能是其抗骨质疏松作用的分子机制之一。

Objective To investigate the effects of phytoestrogenic genistein on OPG/RANKL expression in human osteoblast （HOB）. Methods The expression of osteoprotegerin （OPG）, receptor activator of nuclear factor （NF）-kappaB ligand （RANKL） and estrogen receptor （ER-α, ER-β） was detected by Western blot in human osteoblast. Results ① Genistein with moderate and high level down-regulated the expression of RANKL protein and up-regulated OPG protein in HOB. The estrogen receptor antagonist ICI 182. 780 blocked the effects of 10^-8 mol/L genistein. ②10^-6 mol/L genistein up-regulated the expression of ER-β protein in HOB. The expression of ER-α protein in HOB treated with genistein had no significant difference in comparison to control group （P〉0.05）. ②Ratios of OPG to RANKL were found to be significantly correlated to the genistein levels （r=0. 694, P〈0.05）. Conclusion The effect of genistein is similar to estrogen on the expression of RANKL and OPG in HOB, which is possibly the mechanism on preventing bone mass loss.