Effects of chronic estrogen treatment on modulating age-related bone loss in female mice.
Effects of chronic estrogen treatment on modulating age-related bone loss in female mice.
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慢性雌激素治疗对雌性小鼠年龄相关的骨质流失的影响。
DOI：
10.1002/jbmr.129
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发表时间：
2010-11
影响因子：
6.2
通讯作者：
Khosla, Sundeep
中科院分区：
文献类型：
--
作者：
Syed, Farhan A.;Modder, Ulrike I. L.;Roforth, Matthew;Hensen, Ira;Fraser, Daniel G.;Peterson, James M.;Oursler, Merry Jo;Khosla, Sundeep
虽然雌性小鼠没有相当于更年期，但它们确实经历了生殖衰老。因此，为了分离年龄与雌激素缺乏对年龄相关性骨丢失的影响，我们在6个月龄时对雌性C57/BL 6小鼠进行假手术、卵巢切除或卵巢切除并雌激素替代，并随访至18-22个月龄。切除腰椎和股骨用于分析，分离骨髓造血谱系阴性（lin-）细胞（富含骨祖细胞）用于基因表达研究。处死6个月大的完整对照小鼠以确定基线参数。与年轻小鼠相比，老年/假手术小鼠的腰椎骨体积/总体积（BV/TV）减少了42%，并且在卵巢切除/雌激素治疗的小鼠中保持恒定的雌激素水平并不能防止该部位与年龄相关的骨小梁丢失。相比之下，卵巢切除小鼠的终身雌激素治疗完全防止了老年/假手术小鼠中存在的胫骨骨干皮质体积BMD和厚度的年龄相关性降低。与来自年轻小鼠的细胞相比，来自老年/假手术小鼠的lin-细胞表达成骨细胞分化和增殖标记基因的显著更高的mRNA水平。因此，这些数据表明，在小鼠中，与年龄相关的骨皮质骨的apapapolular骨骼的损失，但不是在脊柱骨小梁的损失，可以通过保持恒定的雌激素水平在整个生命。与年轻小鼠相比，老年小鼠骨髓祖细胞中观察到的成骨细胞分化和增殖标志物基因表达增加可能代表了对持续骨丢失的补偿机制。
While female mice do not have the equivalent of a menopause, they do undergo reproductive senescence. Thus, to dissociate effects of aging versus estrogen deficiency on age-related bone loss, we sham operated, ovariectomized, or ovariectomized and estrogen replaced female C57/BL6 mice at 6 months of age and followed them to age 18-22 months. Lumbar spines and femurs were excised for analysis, and bone marrow hematopoietic lineage negative (lin-) cells (enriched for osteoprogenitor cells) were isolated for gene expression studies. Six month old intact control mice were sacrificed to define baseline parameters. Compared to young mice, aged/sham mice had a 42% reduction in lumbar spine bone volume/total volume (BV/TV), and maintaining constant estrogen levels over life in ovariectomized/estrogen-treated mice did not prevent age-related trabecular bone loss at this site. By contrast, life-long estrogen treatment of ovariectomized mice completely prevented the age-related reduction in cortical volumetric BMD and thickness at the tibial diaphysis present in the aged/sham mice. As compared to cells from young mice, lin- cells from aged/sham mice expressed significantly higher mRNA levels for osteoblast differentiation and proliferation marker genes. These data thus demonstrate that, in mice, age-related loss of cortical bone in the appendicular skeleton, but not loss of trabecular bone in the spine, can be prevented by maintaining constant estrogen levels over life. The observed increase in osteoblastic differentiation and proliferation marker gene expression in progenitor bone marrow cells from aged as compared to young mice may represent a compensatory mechanism in response to ongoing bone loss.
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影响因子：
14.9
作者：
Nygaard V;Hovig E
通讯作者：
Hovig E
影响因子：
3.6
作者：
FELICIO, LS;NELSON, JF;FINCH, CE
通讯作者：
FINCH, CE
影响因子：
4.8
作者：
Hall, JM;McDonnell, DP
通讯作者：
McDonnell, DP
影响因子：
4.1
作者：
Sims, NA;Dupont, S;Baron, R
通讯作者：
Baron, R
影响因子：
20.3
作者：
Riggs, BL;Khosla, S;Melton, LJ
通讯作者：
Melton, LJ