The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts
The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts
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DOI：
10.1016/s8756-3282(02)00953-5
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发表时间：
2003-02-01
期刊：
影响因子：
4.1
通讯作者：
Compston, JE
中科院分区：
文献类型：
--
作者：
Bord, S;Ireland, DC;Compston, JE
雌激素对骨骼的生长和发育以及维持成年期的骨骼健康至关重要。成骨细胞和破骨细胞对雌激素的反应是通过两种高亲和力受体（ER）启动的。成骨细胞合成破骨细胞形成和功能所必需的RANKL（NF-κ B配体的受体激活剂）和其诱饵受体骨保护素（OPG）。为了研究雌激素对人成骨细胞中OPG、RANKL和ER表达的影响，将细胞与生理浓度（10（-10）M）和高剂量（10（-7）M）的17 β-雌二醇培养24和48 h。免疫细胞化学和RT-PCR定量检测蛋白质和相应的mRNA水平。与未处理的细胞相比，10（-10）M（P < 0.05）和10（-7）M（P < 0.01）雌二醇分别使OPG表达在24小时显著增加3倍和7倍。48 h时，细胞增殖率与对照组相似，但差异有统计学意义（P < 0.05）。雌激素作用24 h后RANKL蛋白表达增加（P < 0.05），但48 h后RANKL蛋白表达无明显变化。高剂量雌二醇作用24 h后ER α表达显著增加（P < 0.01），48 h后呈剂量依赖性增加（P < 0.01），而ER β仅在24 h后增加（P < 0.01）。当细胞在雌激素拮抗剂ICI 182，780存在下培养时，雌激素诱导的ER、OPG和RANKL蛋白表达被废除。24 h时的mRNA水平显示低剂量组对RANKL有显著抑制作用，但高剂量组无此作用。雌激素可上调ERα mRNA的表达，但不上调ERβ的表达。我们的研究结果表明，雌激素可能发挥其抗骨吸收的作用，至少部分，通过刺激ER和OPG在成骨细胞的表达。(C)2003 Elsevier Science（美国）。All rights reserved.
Estrogen is essential for bone growth and development and for the maintenance of bone health in adulthood. The cellular responses of osteoblasts and osteoclasts to estrogen are initiated via two high-affinity receptors (ERs). Osteoblasts synthesize RANKL (receptor activator of NF-kappaB ligand), necessary for osteoclast formation and function, and osteoprotegerin (OPG), its decoy receptor. To investigate the effects of estrogen on the expression of OPG, RANKL, and ERs in human osteoblasts, cells were cultured with physiological (10(-10) M) and high-dose (10(-7) M) 17beta-estradiol for 24 and 48 h. Proteins and corresponding mRNA levels were quantitatively determined by immunocytochemistry and RT-PCR. OPG expression was significantly increased three- and sevenfold at 24 h with 10(-10) M (P < 0.05) and 10(-7) M (P < 0.01) estradiol, respectively, compared to untreated cells. Similar but smaller increases were seen at 48 h (P < 0.05). Osteoblasts treated with estradiol demonstrated increased RANKL protein expression at 24 h (P < 0.05), but this was not maintained at 48 h. ERalpha expression was significantly increased by high-dose estradiol (P < 0.01) at 24 h and dose-dependently increased at 48 h (P < 0.01), while ERbeta was only increased at 24 h (P < 0.01). The estrogen-induced protein expression of ER, OPG, and RANKL was abrogated when cells were cultured in the presence of the estrogen antagonist ICI 182,780. mRNA levels at 24 h demonstrated a significant suppression of RANKL with the low-dose but not the high dose. ERα mRNA but not ERβ expression was up-regulated by estrogen. Our results suggest that estrogen may exert its anti-resorptive effects on bone, at least in part, by stimulating ER and OPG expression in osteoblasts. (C) 2003 Elsevier Science (USA). All rights reserved.