摘要
目的研究脱氢表雄酮(DHEA)对成骨细胞雌激素受体(ER)亚型的调节及防治绝经后骨质疏松的作用机制。方法取新生2～4 d BALB/c小鼠颅骨,用酶消化法进行成骨细胞原代培养并鉴定。取原代培养的成骨细胞,模仿雌激素撤退现象后,给予不同时间1×10-7mol·L-1的DHEA培养,透射电镜观察细胞器的变化,RT-PCR分析成骨细胞护骨素(OPG)/破骨细胞分化因子(RANKL),ER亚型的表达;同时分析ER亚型与OPG生成的相关性。结果1×10-7mol·L-1的DHEA使成骨细胞的细胞器更为丰富,糖原减少,高尔基体发达且分层增多;对成骨细胞ERα的表达无明显影响,却增高OPG/RANKL,ERβ的表达(均为P<0.01),二者的表达水平呈明显正相关(P<0.01)。结论DHEA能够增高OPG/RANKL的表达,从而抑制骨的吸收;其作用机制与ERβ的上调有关。
Abstract
OBJECTIVE To investigate the up-regulation of ERβ in osteoblast and the mechanism for preventing and curing postmenopausal osteoporosis with dehydroepiandrosterone(DHEA).METHODS Murine osteoblasts(OBs) from calvaria of neonatal BALB/c mice were cultured and treated with 1×10-7 mol·L-1 DHEA at different time after the estrogen withdrawal.The biological characteristics of OBs were evaluated by transmission electroscope.The mRNA level of osteoprotegerin(OPG)/receptor activator of NF-κB ligand(RANKL) and estrogen receptor(ER) isoforms were detected by RT-PCR.The correlation between ER isoform and OPG/RANKL was analyzed,too.RESULTS With the action of 1×10-7 mol·L-1 DHEA.The OBs had more organelles and less glycogen.The expression of OPG/RANKL mRNA(P<0.01) and ERβ mRNA(P<0.01) in OBs was improved and the ratio of OPG/RANKL mRNA was positively related to the expression of ERβ mRNA(P<0.01).No significance was obtained in the expression of ERα.CONCLUSION DHEA can improve the expression of OPG/RANKL so as to inhibit the bone resorption of OC,which is mediated by the up-regulation of ERβ in OBs.
关键词
脱氢表雄酮 /
成骨细胞 /
成骨细胞护骨素 /
雌激素受体
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Key words
dehydroepiandrosterone /
osteoblast /
osteoprotegerin /
estrogen receptor
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王玉东;童剑倩;罗来敏;李大金.
脱氢表雄酮对成骨细胞ERβ的上调节作用[J]. 中国药学杂志, 2006, 41(07): 509-511
WNG Yu-dong;TONG Jin-qin;LUO Li-min;LI D-jin.
Up-regulation of ERβ in Murine Osteoblasts with the Action of Dehydroepiandrosterone [J]. Chinese Pharmaceutical Journal, 2006, 41(07): 509-511
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参考文献
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脚注
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基金
国家自然科学基金资助项目(30472259);上海市卫生局青年基金(044Y06)
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