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雌激素改善维生素D受体基因敲除雌性小鼠的骨、钙代谢

李冰燕, 童建, 张增利

苏州大学放射医学与公共卫生学院.江苏,苏州 215123

摘要

以维生素D受体基因敲除雌性小鼠为模型，研究雌激素对骨、钙代谢的调节作用。外源性给予雌二醇一个月后，观察小鼠血钙水平的变化，同时测定小鼠骨密度，并利用胫骨非脱钙yon Kossa染色观察钙化的骨小梁和未钙化的类骨质面积的变化。结果显示，外源性给予雌二醇一个月后，维生素D受体基因敲除小鼠的血钙水平，从（2.10±0.37）mmol／L上升到（2.80±0.41）mmol/L（{sl P}<0.05）；骨密度从（0.037±0.006）g/cm~(2)增高N（0.048±0.007）g/cm~(2)，显著改善（{sl P}<0.05）；钙化骨小梁面积显著增加，未钙化的类骨质面积显著缩小。结果提示，外源性雌二醇对骨、钙代谢具有非依赖于维生素D的正向调节作用。

关键词： 维生素D受体; 雌激素; 钙平衡; 骨骼矿化

Exogenous estrogen improved calcium homeostasis and skeletal mineralization in vitamin D receptor gene knockout female mice

Li Bingyan, Tong Jian, Zhang Zengli

Radiation Medical and Public School of Soochow University.Suzhou 215123,Jiangsu

Abstract

It is well known that estrogen can inhibit bone absorption, decrease bone turnover and preserve bone mass. Some studies indicated that the effect of estrogen on calcium and bone is relative to vitamin D system, while others also reported that this effect of estrogen is independent of vitamin D. The genomic effect of 1α, 25（OH）_(2)D_(3) is mediated by the nuclear vitamin D receptor （VDR） in a ligand-dependent manner. Hypocalcemia, hyperparathyroidism and osteomalacia are developed in VDR gene knockout mice. To determine whether the effect of estrogen on calcium and bone is dependent on VDR, this study examined the effect of exogenous estrogen on calcium and bone homeostasis in VDR gene knockout mice. Male and female wild type （WT） and VDR gene knockout heterozygous mice were mated each other and the genotyping of their offsprings were determined by PCR. At age of 21-day, WT and knockout mice were weaned and treated by one of three different regimens： （1） WT-vehicle group： the WT mice were injected with normal saline; （2） VDR KO-vehicle group： the VDR gene knockout mice were injected with normal saline; （3） VDR KO-E group： the VDR gene knockout mice were subcutaneously injected with estradiol, 0.2 #mu#g per mouse, once daily for 1 month. The bone mineral density （BMD） of mice was measured using dual-energy X-ray absorptiometry. All mice were sacrificed at age of 50-day. Blood was taken by heart puncture under anesthesia and serum calcium was measured by autoanalyser.Tibiae were removed, fixed and embedded with the methylmethacrylate （MMA）, and undecalcified sections were cut. These sections were stained for mineral with the yon Kossa staining procedure and counterstalned with toluidine blue. Static histomorphometric analyses were performed on those stained sections. The results showed that the serum calcium level was （2.10±0.37） mmol/L in the VDR KO-vehicle mice and rose to （2.80±0.41） mmol/L in the VDR KO-E mice although it was still lower than WT-vehicle mice [（3.10±0.48） mmol/L]. BMD and mineralized trabeculer volume were increased significantly in VDR KO-E group compared with that in VDR KO-vehicle group. These results suggest that exogenous estrogen can improve calcium absorption and skeletal mineralization in a VDR-independent manner.

Key words: vitamin D receptor;Estrogen;calcium homeostasis;skeleton mineralization

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引用本文：

李冰燕, 童建, 张增利. 雌激素改善维生素D受体基因敲除雌性小鼠的骨、钙代谢[J]. 生理学报 2006; 58 (6): .

Li Bingyan, Tong Jian, Zhang Zengli. Exogenous estrogen improved calcium homeostasis and skeletal mineralization in vitamin D receptor gene knockout female mice. Acta Physiol Sin 2006; 58 (6): (in Chinese with English abstract).