Comparison of skeletal effects of ovariectomy versus chemically induced ovarian failure in mice.
Comparison of skeletal effects of ovariectomy versus chemically induced ovarian failure in mice.
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DOI：
10.1359/jbmr.080309
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发表时间：
2008-08
期刊：
影响因子：
--
通讯作者：
Hoyer PB
中科院分区：
文献类型：
--
作者：
Wright LE;Christian PJ;Rivera Z;Van Alstine WG;Funk JL;Bouxsein ML;Hoyer PB
与绝经相关的骨质流失导致骨骼脆弱性和骨折风险增加。相关的动物模型可用于评估卵巢功能衰竭对骨丢失的影响。使用化学4-乙烯基环己烯二环氧化物（VCD）开发了一种化学诱导的绝经模型，其中小鼠逐渐经历卵巢衰竭但保留残留的卵巢组织。本研究旨在比较VCD诱导的卵巢功能衰竭与卵巢切除术（OVX）相关的骨骼效应。对年幼（28天）C57 Bl/6 Hsd雌性小鼠每天给予溶媒或VCD（160 mg/kg/d，IP），持续15天（n = 6-7只/组），并通过阴道细胞学监测卵巢衰竭。在VCD诱导的卵巢衰竭的平均年龄（给药开始后约16周），对不同组小鼠进行卵巢切除术（OVX，n = 8）。在卵巢功能衰竭和OVX后3个月用DXA测量脊柱骨密度（SpBMD）。在卵巢衰竭或OVX后15个月处死小鼠，通过μCT离体评价骨结构。在OVX小鼠中，SpBMD在OVX后1个月低于对照组，而在VCD治疗的小鼠中，SpBMD直到卵巢衰竭后2.9个月才低于对照组（p < 0.05）。VCD诱导的卵巢衰竭和OVX均导致骨小梁结构明显恶化，OVX小鼠的影响略大。在股骨干，皮质骨面积和厚度在VCD小鼠和对照组之间没有差异，但在OVX组与两组相比有所减少（p < 0.05）。与对照组相比，VCD处理小鼠的循环雄烯二酮水平保持不变，但OVX小鼠的循环雄烯二酮水平降低（p < 0.001）。这些发现支持（1）VCD诱导的卵巢衰竭导致骨小梁退化，（2）骨丢失被残留的卵巢组织减弱，特别是在骨干皮质骨中，和（3）VCD小鼠模型可以是相关骨病研究中自然绝经的相关模型。
Bone loss associated with menopause leads to an increase in skeletal fragility and fracture risk. Relevant animal models can be useful for evaluating the impact of ovarian failure on bone loss. A chemically induced model of menopause in which mice gradually undergo ovarian failure yet retain residual ovarian tissue has been developed using the chemical 4-vinylcyclohexene diepoxide (VCD). This study was designed to compare skeletal effects of VCD-induced ovarian failure to those associated with ovariectomy (OVX). Young (28 day) C57Bl/6Hsd female mice were dosed daily with vehicle or VCD (160 mg/kg/d, IP) for 15 days (n = 6–7/group) and monitored by vaginal cytology for ovarian failure. At the mean age of VCD-induced ovarian failure (∼6 wk after onset of dosing), a different group of mice was ovariectomized (OVX, n = 8). Spine BMD (SpBMD) was measured by DXA for 3 mo after ovarian failure and OVX. Mice were killed ∼5 mo after ovarian failure or OVX, and bone architecture was evaluated by μCT ex vivo. In OVX mice, SpBMD was lower than controls 1 mo after OVX, whereas in VCD-treated mice, SpBMD was not lower than controls until 2.9 mo after ovarian failure (p < 0.05). Both VCD-induced ovarian failure and OVX led to pronounced deterioration of trabecular bone architecture, with slightly greater effects in OVX mice. At the femoral diaphysis, cortical bone area and thickness did not differ between VCD mice and controls but were decreased in OVX compared with both groups (p < 0.05). Circulating androstenedione levels were preserved in VCD-treated mice but reduced in OVX mice relative to controls (p < 0.001). These findings support that (1) VCD-induced ovarian failure leads to trabecular bone deterioration, (2) bone loss is attenuated by residual ovarian tissue, particularly in diaphyseal cortical bone, and (3) the VCD mouse model can be a relevant model for natural menopause in the study of associated bone disorders.
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影响因子：
3.6
作者：
Mayer, LP;Devine, PJ;Hoyer, PB
通讯作者：
Hoyer, PB
影响因子：
4.8
作者：
Perrien, Daniel S.;Akel, Nisreen S.;Gaddy, Dana
通讯作者：
Gaddy, Dana
影响因子：
3.6
作者：
Hu, XM;Christian, PJ;Hoyer, PB
通讯作者：
Hoyer, PB
DOI：
10.1097/01.gme.0000191883.59799.2e
发表时间：
2006-05-01
影响因子：
2.7
作者：
Lohff, Jessica C.;Christian, Patricia J.;Hoyer, Patricia B.
通讯作者：
Hoyer, Patricia B.
影响因子：
4
作者：
Plant, A;Samuels, A;Tobias, JH
通讯作者：
Tobias, JH