The Role of Estrogen Receptor α in Growth Plate Cartilage for Longitudinal Bone Growth

被引:63
作者
Borjesson, Anna E. [1 ]
Lagerquist, Marie K. [1 ]
Liu, Chen [2 ]
Shao, Ruijin [3 ]
Windahl, Sara H. [1 ]
Karlsson, Camilla [4 ]
Sjogren, Klara [1 ]
Moverare-Skrtic, Sofia [1 ]
Antal, Maria Christina [4 ]
Krust, Andree [5 ]
Mohan, Subburaman [6 ]
Chambon, Pierre [5 ]
Savendahl, Lars [2 ]
Ohlsson, Claes [1 ]
机构
[1] Univ Gothenburg, Ctr Bone & Arthrit Res, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden
[2] Karolinska Inst, Pediat Endocrinol Unit, Dept Womans & Childrens Hlth, Stockholm, Sweden
[3] Sahlgrens Acad, Dept Physiol Endocrinol, Inst Neurosci & Physiol, Gothenburg, Sweden
[4] Sahlgrens Univ Hosp, Inst Lab Med, Dept Clin Chem & Transfus Med, SE-41345 Gothenburg, Sweden
[5] IGBMC, Illkirch Graffenstaden, France
[6] Jerry L Pettis VA Med Ctr, Musculoskeletal Dis Ctr, Loma Linda, CA USA
基金
瑞典研究理事会;
关键词
BONE ESTROGEN RECEPTOR; GROWTH; GROWTH PLATE CARTILAGE; ER-ALPHA; FACTOR-I; CHONDROCYTE DIFFERENTIATION; SKELETAL GROWTH; AROMATASE; EXPRESSION; BETA; TESTOSTERONE; ESTRADIOL; GENE;
D O I
10.1002/jbmr.156
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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
引用
收藏
页码:2414 / 2424
页数:11
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