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Simvastatin induces estrogen receptor-alpha expression in bone, restores bone loss, and decreases ER alpha expression and uterine wet weight in ovariectomized rats
Li, Xu; Song, Quan-Sheng; Wang, Jing-Ying; Leng, Hui-Jie; Chen, Zhong-Qiang; Liu, Zhong-Jun; Dang, Geng-Ting; Song, Chun-Li
关键词Simvastatin Osteoporosis Estrogen Receptor-Alpha (Er Alpha) Bone Uterus
刊名JOURNAL OF BONE AND MINERAL METABOLISM
2011-07-01
DOI10.1007/s00774-010-0231-y
29期:4页:396-403
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism ; Medicine, Research & Experimental
研究领域[WOS]Endocrinology & Metabolism ; Research & Experimental Medicine
关键词[WOS]HYPERCHOLESTEROLEMIC POSTMENOPAUSAL WOMEN ; HORMONE-REPLACEMENT THERAPY ; ENDOMETRIAL STROMAL CELLS ; NEGATIVE BREAST-CANCER ; MINERAL DENSITY ; IN-VITRO ; STATINS ; GROWTH ; INHIBITORS ; ESTRADIOL
英文摘要

We previously reported that simvastatin induces estrogen receptor-alpha (ER alpha) in murine bone marrow stromal cells in vitro. In this study, we investigated the effect of simvastatin on ER alpha expression in bone and uterus in ovariectomized (OVX) rats and evaluated bone mass, bone strength, and uterine wet weight. Three-month-old Sprague-Dawley female rats received OVX or sham operation. Six weeks later, the rats were treated orally with simvastatin (5 or 10 mg/kg/day), or intraperitoneally with 17-beta-estradiol (E(2)) or a combination of simvastatin and E(2) for 6 weeks. Uterine wet weight, bone mineral density (BMD) of lumbar vertebrae, biomechanics of lumbar vertebrae, and induction of ER alpha expression in the bone and uterus were analyzed. The 6-week simvastatin treatment improved lumbar vertebral BMD and boosted biomechanical performance of the vertebral body compared to the OVX control, suggesting that simvastatin can treat osteoporosis caused by estrogen deficiency. More interestingly, simvastatin could increase ER alpha expression and synergy with estradiol in bone while antagonizing estradiol in the uterus, along with uterus atrophy and uterine wet weight decreases. In conclusion, these data suggest that simvastatin exert opposing modulatory effects on ER alpha expression on bone and uterus in ovariectomized rats, inducing ER alpha expression and synergy with estrogen to perform anabolic effects on the bones while decreasing E2 efficacy and uterine wet weight. This finding may be helpful to explain the mechanism of statin treatment in osteoporosis caused by estrogen deficiency.

语种英语
WOS记录号WOS:000292607100002
项目编号30300352 ; 30772200
资助机构National Natural Science Foundation of China
引用统计
被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56529
专题北京大学第三临床医学院_骨科
作者单位Peking Univ, Hosp 3, Dept Orthoped, Beijing 100191, Peoples R China
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GB/T 7714
Li, Xu,Song, Quan-Sheng,Wang, Jing-Ying,et al. Simvastatin induces estrogen receptor-alpha expression in bone, restores bone loss, and decreases ER alpha expression and uterine wet weight in ovariectomized rats[J]. JOURNAL OF BONE AND MINERAL METABOLISM,2011,29(4):396-403.
APA Li, Xu.,Song, Quan-Sheng.,Wang, Jing-Ying.,Leng, Hui-Jie.,Chen, Zhong-Qiang.,...&Song, Chun-Li.(2011).Simvastatin induces estrogen receptor-alpha expression in bone, restores bone loss, and decreases ER alpha expression and uterine wet weight in ovariectomized rats.JOURNAL OF BONE AND MINERAL METABOLISM,29(4),396-403.
MLA Li, Xu,et al."Simvastatin induces estrogen receptor-alpha expression in bone, restores bone loss, and decreases ER alpha expression and uterine wet weight in ovariectomized rats".JOURNAL OF BONE AND MINERAL METABOLISM 29.4(2011):396-403.
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