脱氢表雄酮对成骨细胞ERβ的上调节作用

Up-regulation of ERβ in Murine Osteoblasts with the Action of Dehydroepiandrosterone

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—4dBALB／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1×100mol·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。

OBJECTIVE To investigate the up-regulation of ERβ in osteoblast and the mechanism for preventing and curing postmenopausal osteoporosis with dehydroepiandrosterone （DHEA）, METHOI/S Mufine osteoblasts （OBs） from calvaria of neonatal BALB/c mice were cuhured 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 （0PG）/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 organdies 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 ERa. 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.