Bone phenotype of the aromatase deficient mouse.

Bone phenotype of the aromatase deficient mouse.
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芳香酶缺陷小鼠的骨表型。

DOI:
10.1016/s0960-0760(01)00130-3
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发表时间:
2001
期刊:
The Journal of steroid biochemistry and molecular biology
影响因子:
--
通讯作者:
Simpson,ER
Simpson,ER
中科院分区:
--
文献类型:
--
作者:
Oz,OK;Hirasawa,G;Lawson,J;Nanu,L;Constantinescu,A;Antich,PP;Mason,RP;Tsyganov,E;Parkey,RW;Zerwekh,JE;Simpson,ER

文献摘要

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雌激素对正常的骨骼生长和代谢很重要。其机制尚不完全清楚。因此,我们进行了表征的芳香化酶(ArKO)缺陷小鼠的骨骼表型。新生儿的骨骼形态未见异常。成年ArKO小鼠显示股骨长度减少和峰值骨矿物质密度(BMD)降低,雌性中到7月龄时骨丢失加速。磁共振显微镜(MR)和microCT(μCT)成像显示ArKO雌性动物松质骨连接性降低,松质骨体积减少。ArKO雌性动物的骨形成率(BFR)增加,而ArKO雄性动物的骨形成率降低。雌二醇治疗逆转了这些变化。雌二醇在男性骨骼中的合成代谢作用得到了18-F−正电子发射断层扫描(PET)成像的支持,该成像清楚地表明脊髓摄取减少,但雌二醇治疗后显著增加。血清IGF-1水平在年轻的雌性ArKO小鼠中较高,但在年轻的ArKO雄性中较低。尽管存在升高的血清IGF 1,但ArKO雌性中BMD降低表明其他机制也起作用。成年雌性ArKO骨髓细胞中B细胞淋巴细胞生成增加。这些结果表明,ArKO小鼠显示雌激素缺乏对骨生长、质量、代谢、微结构和造血微环境的影响。
Estrogens are important for normal bone growth and metabolism. The mechanisms are incompletely understood. Thus, we have undertaken characterization of the skeletal phenotype of aromatase (ArKO) deficient mice. No abnormalities have been noted in skeletal patterning in newborns. Adult ArKO mice show decreased femur length and decreased peak Bone Mineral Density (BMD) with accelerated bone loss by 7 months of age in females. Magnetic resonance microscopy (MR) and microCT (μCT) imaging disclosed decreased cancellous connectivity and reduced cancellous bone volume in ArKO females. Bone formation rate (BFR) is increased in ArKO females and decreased in ArKO males. Estradiol therapy reverses these changes. This anabolic effect of estradiol in the male skeleton is supported by 18-F−Positron Emission Tomography (PET) imaging, which clearly demonstrates decreased spinal uptake, but marked increase after estradiol therapy. Serum IGF-1 levels are high in young female ArKO mice but low in young ArKO males. The reduced BMD in ArKO females, despite the presence of elevated serum IGF 1, suggests that other mechanism(s) are operative. There is increased B-cell lymphopoiesis in adult female ArKO bone marrow cells. These results show that ArKO mice show the effects of estrogen deficiency on bone growth, mass, metabolism, microarchitecture and the hematopoietic microenvironment.