Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells.
Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells.
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DOI：
10.1210/endo.140.9.7131
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发表时间：
1999-09
期刊：
影响因子：
4.8
通讯作者：
L. Hofbauer;S. Khosla;C. Dunstan;D. Lacey;T. Spelsberg;B. Riggs
中科院分区：
文献类型：
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作者：
L. Hofbauer;S. Khosla;C. Dunstan;D. Lacey;T. Spelsberg;B. Riggs
雌激素对骨细胞的抗吸收作用的旁分泌介质的身份是有争议的。骨保护素（OPG）是肿瘤坏死因子（TNF）受体（TNF-R）超家族的一个可溶性成员，由成骨细胞分泌，通过与破骨细胞生成所需的配体OPG-L结合并中和而发挥作用。OPG给药于卵巢切除大鼠时可防止骨丢失，在基因敲除小鼠中消融时可诱导骨质疏松症，在转基因小鼠中过表达时可诱导骨硬化症。在有条件永生化的人成骨细胞hFOB/ER-3和hFOB/ER-9细胞系中，分别含有生理浓度约800和约8，000个功能性雌激素受体（ER）/细胞核，我们发现17 β-雌二醇剂量和时间依赖性地增加OPG mRNA和蛋白水平，最高水平分别为370%和320（P < 0.001）;与“纯”抗雌激素ICI 182，780共同治疗完全消除了这些作用。17 β-雌二醇还剂量依赖性地增加了正常人成骨细胞（约400 ER/核）中OPG mRNA和蛋白水平，分别增加了60%和73%。因此，雌激素促进成骨细胞分泌OPG可能在雌激素对骨的抗吸收作用中起主要作用。
The identity of the paracrine mediator(s) of the antiresorptive action of estrogen on bone cells is controversial. Osteoprotegerin (OPG) was recently identified as a soluble member of the tumor necrosis factor (TNF) receptor (TNF-R) superfamily that is secreted by osteoblast lineage cells and acts by binding to and neutralizing its cognate ligand, OPG-L, a required factor for osteoclastogenesis. OPG prevents bone loss when administered to ovariectomized rats, induces osteoporosis when ablated in knock-out mice, and induces osteopetrosis when overexpressed in transgenic mice. In conditionally immortalized, human osteoblastic hFOB/ER-3 and hFOB/ER-9 cell lines containing physiological concentrations of approximately 800 and approximately 8,000 functional estrogen receptors (ER)/nucleus, respectively, we found that 17beta-estradiol dose- and time-dependently increased OPG mRNA and protein levels to maximal levels of 370% and 320%, respectively (P < 0.001); co-treatment with the "pure" antiestrogen ICI 182,780 abrogated these effects completely. 17beta-Estradiol also dose-dependently increased OPG mRNA and protein levels in normal human osteoblasts with approximately 400 ER/nucleus by 60% and 73%, respectively. Thus, estrogen enhancement of OPG secretion by osteoblastic cells may play a major role in the antiresorptive action of estrogen on bone.