The Role of Estrogen Receptor α in Growth Plate Cartilage for Longitudinal Bone Growth
The Role of Estrogen Receptor α in Growth Plate Cartilage for Longitudinal Bone Growth
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DOI：
10.1002/jbmr.156
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发表时间：
2010-12-01
影响因子：
6.2
通讯作者：
Ohlsson, Claes
中科院分区：
文献类型：
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作者：
Borjesson, Anna E.;Lagerquist, Marie K.;Ohlsson, Claes
雌激素在性成熟早期促进骨骼生长，而青春期后期的高雌二醇水平导致人类生长板融合。雌激素对骨骼生长的影响是直接通过生长板软骨中的雌激素受体（ER）介导还是间接通过其他机制，如生长激素/胰岛素样生长因子1 （GH/IGF-1）轴介导，目前尚不清楚。尽管ERa完全失活的小鼠显示出与GH/IGF-1轴改变相关的纵向骨生长受到影响，成年小鼠经高剂量雌二醇处理后，生长板高度降低，这是由于对照组小鼠生长板软骨细胞增殖减弱，但在软骨特异性ER α(-/-)小鼠中没有这种现象。成年软骨特异性ER α(-/-)小鼠在4个月后继续生长，而对照组小鼠的生长受到限制。我们得出结论，在性成熟早期，生长板软骨中的ERa对骨骼生长并不重要。相反，大剂量雌二醇对降低成年小鼠生长板高度和减少老年小鼠纵向骨生长至关重要(C) 2010年美国骨与矿物研究协会
Estrogens enhance skeletal growth during early sexual maturation, whereas high estradiol levels during late puberty result in growth plate fusion in humans Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis To determine the role of ER alpha in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERa Although mice with total ERa inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-1 axis, the skeletal growth was normal during sexual maturation in mice with cartilage-specific ERa inactivation High-dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ER alpha(-/-) mice Adult cartilage-specific ER alpha(-/-) mice continued to grow after 4 months of age, whereas growth was limited in control mice, resulting in increased femur length in 1-year-old cartilage-specific ER alpha(-/-) mice compared with control mice We conclude that during early sexual maturation, ERa in growth plate cartilage is not important for skeletal growth In contrast, it is essential for high-dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice (C) 2010 American Society for Bone and Mineral Research