Dynamic changes of femur microarchitecture in ovariectomized mice

Yu QIU; Yueyang ZHAO; Zhimin LONG; Kejian WANG; Ling XU; Guiqiong HE

doi:10.16016/j.1000-5404.202103089

您当前的位置：

首页 >

文章列表页 >

Dynamic changes of femur microarchitecture in ovariectomized mice

更新时间：2026-01-09

- Dynamic changes of femur microarchitecture in ovariectomized mice
- Journal of Third Military Medical University Vol. 43, Issue 17, Pages: 1627-1633(2021)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81671257);the Construction Program of Innovative Research Groups of Chongqing Colleges and Universities(CXTDG201602006)
- DOI：10.16016/j.1000-5404.202103089
  CLC：
- Received：10 March 2021，
  
  Published：15 September 2021
- 稿件说明：
移动端阅览
Yu QIU, Yueyang ZHAO, Zhimin LONG, et al. Dynamic changes of femur microarchitecture in ovariectomized mice[J]. Journal of Third Military Medical University, 2021, 43(17): 1627-1633.
DOI：

Yu QIU, Yueyang ZHAO, Zhimin LONG, et al. Dynamic changes of femur microarchitecture in ovariectomized mice[J]. Journal of Third Military Medical University, 2021, 43(17): 1627-1633. DOI： 10.16016/j.1000-5404.202103089.

摘要

目的

探究去卵巢骨质疏松小鼠术后不同时期股骨微结构的动态变化。

方法

8周龄C57雌性小鼠分为去卵巢组（ovariectomy，OVX）和假手术组（sham ovariectomy

Sham），并根据术后不同时间将每组小鼠又分为1周、1个月及3个月组，分别代表绝经早、中、晚期。称质量后取小鼠股骨进行HE染色、免疫组织化学染色及Micro-CT扫描分析，评估各组股骨远端松质骨、股骨中段皮质骨微结构及成骨相关蛋白水平变化。

结果

小鼠松质骨形态参数：与Sham组相比，OVX组术后1周骨微结构未见明显破坏，术后1~3个月骨小梁断裂，骨髓腔增大，CT骨参数除Tb.Th无明显变化外

0.05)，BV/TV，Tb.N和Tb.Sp均出现显著改变（

0.01）；Sham组中，直到术后3个月才出现较1周组骨量显著减少的表现（

0.01）；OVX各组中骨丢失情况随时间增加而加重（

0.05，

0.01）。Runx2表达水平与Micro-CT松质骨分析结果基本一致。皮质骨形态参数：各时段OVX组均未出现较Sham组的明显差异（P

0.05）。

结论

8周龄C57小鼠在OVX术后1周至1个月松质骨微结构明显受损，早于皮质骨变化，可作为骨质疏松病理机制和防治研究的重点阶段。

Abstract

Objective

To explore the dynamic changes of femur microstructure in ovariectomized osteoporosis mice at different stages.

Methods

Female C57 mice (8 weeks old) were randomly divided into sham-operation (Sham) and ovariectomy (OVX) groups. Each group was subdivided into 1-week

1-month and 3-month subgroups on the basis of different postoperative time

which representeing early

middle and late menopause

respectively. The femurs were extracted for HE staining

immunohistochemistry and micro-CT analysis

and the changes in the bone microstructure of cancellous bone in the distal femurs

cortical bone in the middle femurs and the levels of osteogenic associated proteins in each group were evaluated.

Results

Compared with the Sham group

the bone microstructure of the OVX group showed no significant destruction at 1 week after operation

trabecula fracture and bone marrow cavity enlargement from 1 month to 3 months after operation

and significant changes in CT bone parameters BV/TV

Tb.N and Tb.Sp (

0.01

0.001) except Tb.Th (P

0.05). In the Sham group

the bone mass was significantly reduced until 3 months after operation compared with that in the 1-week group (

0.01). Bone loss in the OVX groups was worsened in a time dependent manner (

0.05

0.01

0.001). The expression level of Runx2 by immunohistochemistry was consistent with

the results of micro-CT analysis. No significant differences were found in morphologic indices of cortical bone between the Sham subgroups and the OVX subgroups (P

0.05).

Conclusion

Trabecular bone microarchitecture is impaired progressively after OVX operation in 8-week-old C57 mice from 1 week to 1 month

prior to cortical bone. This period can be regarded as the key time for studies on pathogenesis and prevention and treatment of osteoporosis.

关键词

Keywords

references

COMPSTON J E MCCLUNG M R LESLIE W D Osteoporosis Lancet 2019 393 10169 364 376 10.1016/S0140-6736(18)32112-3 COMPSTON J E, MCCLUNG M R, LESLIE W D. Osteoporosis[J]. Lancet, 2019, 393(10169): 364-376. DOI: 10.1016/S0140-6736(18)32112-3.

YU F XIA W B The epidemiology of osteoporosis, associated fragility fractures, and management gap in China Arch Osteoporos 2019 14 1 1 20 10.1007/s11657-018-0549-y YU F, XIA W B. The epidemiology of osteoporosis, associated fragility fractures, and management gap in China[J]. Arch Osteoporos, 2019, 14(1): 1-20. DOI: 10.1007/s11657-018-0549-y.

AZIZIYEH R MO A HABIB M The burden of osteoporosis in four Latin American countries: Brazil, Mexico, Colombia, and Argentina J Med Econ 2019 22 7 638 644 10.1080/13696998.2019.1590843 AZIZIYEH R, MO A, HABIB M, et al . The burden of osteoporosis in four Latin American countries: Brazil, Mexico, Colombia, and Argentina[J ] . J Med Econ, 2019, 22(7): 638-644. DOI: 10.1080/13696998.2019.1590843.

BONUCCI E BALLANTI P Osteoporosis-bone remodeling and animal models Toxicol Pathol 2014 42 6 957 969 10.1177/0192623313512428 BONUCCI E, BALLANTI P. Osteoporosis-bone remodeling and animal models[J]. Toxicol Pathol, 2014, 42(6): 957-969. DOI: 10.1177/0192623313512428.

CONSORTIUM M G S WATERSTON R H LINDBLAD-TOH K Initial sequencing and comparative analysis of the mouse genome Nature 2002 420 6915 520 562 10.1038/nature01262 CONSORTIUM M G S, WATERSTON R H, LINDBLAD-TOH K, et al . Initial sequencing and comparative analysis of the mouse genome[J ] . Nature, 2002, 420(6915): 520-562. DOI: 10.1038/nature01262.

CAPECCHI M R Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century Nat Rev Genet 2005 6 6 507 512 10.1038/nrg1619 CAPECCHI M R. Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century[J]. Nat Rev Genet, 2005, 6(6): 507-512. DOI: 10.1038/nrg1619.

HAN S K KIM D LEE H Divergence of noncoding regulatory elements explains gene-phenotype differences between human and mouse orthologous genes Mol Biol Evol 2018 35 7 1653 1667 10.1093/molbev/msy056 HAN S K, KIM D, LEE H, et al . Divergence of noncoding regulatory elements explains gene-phenotype differences between human and mouse orthologous genes[J ] . Mol Biol Evol, 2018, 35(7): 1653-1667. DOI: 10.1093/molbev/msy056.

MAYNARD R D ACKERT-BICKNELL C L Mouse models and online resources for functional analysis of osteoporosis genome-wide association studies Front Endocrinol 2019 10 277 10.3389/fendo.2019.00277 MAYNARD R D, ACKERT-BICKNELL C L. Mouse models and online resources for functional analysis of osteoporosis genome-wide association studies[J]. Front Endocrinol, 2019, 10: 277. DOI: 10.3389/fendo.2019.00277.

WONG K C PANG W Y WANG X L Drynaria fortunei-derived total flavonoid fraction and isolated compounds exert oestrogen-like protective effects in bone Br J Nutr 2013 110 3 475 485 10.1017/S0007114512005405 WONG K C, PANG W Y, WANG X L, et al . Drynaria fortunei-derived total flavonoid fraction and isolated compounds exert oestrogen-like protective effects in bone[J ] . Br J Nutr, 2013, 110(3): 475-485. DOI: 10.1017/S0007114512005405.

YANG L L ZHANG B LIU J J Protective effect of acteoside on ovariectomy-induced bone loss in mice Int J Mol Sci 2019 20 12 2974 10.3390/ijms20122974 YANG L L, ZHANG B, LIU J J, et al . Protective effect of acteoside on ovariectomy-induced bone loss in mice[J ] . Int J Mol Sci, 2019, 20(12): 2974. DOI: 10.3390/ijms20122974.

LIANG X X HOU Z Q XIE Y L Icariin promotes osteogenic differentiation of bone marrow stromal cells and prevents bone loss in OVX mice via activating autophagy J Cell Biochem 2019 120 8 13121 13132 10.1002/jcb.28585 LIANG X X, HOU Z Q, XIE Y L, et al . Icariin promotes osteogenic differentiation of bone marrow stromal cells and prevents bone loss in OVX mice via activating autophagy[J ] . J Cell Biochem, 2019, 120(8): 13121-13132. DOI: 10.1002/jcb.28585.

DING Y JIANG H J MENG B Y Sweroside-mediated mTORC1 hyperactivation in bone marrow mesenchymal stem cells promotes osteogenic differentiation J Cell Biochem 2019 120 9 16025 16036 10.1002/jcb.28882 DING Y, JIANG H J, MENG B Y, et al . Sweroside-mediated mTORC1 hyperactivation in bone marrow mesenchymal stem cells promotes osteogenic differentiation[J ] . J Cell Biochem, 2019, 120(9): 16025-16036. DOI: 10.1002/jcb.28882.

JANG S A HWANG Y H KIM T Anti-osteoporotic and anti-adipogenic effects of the water extract of Drynaria Roosii Nakaike in ovariectomized mice fed a high-fat diet Molecules 2019 24 17 3051 10.3390/molecules24173051 JANG S A, HWANG Y H, KIM T, et al . Anti-osteoporotic and anti-adipogenic effects of the water extract of Drynaria Roosii Nakaike in ovariectomized mice fed a high-fat diet[J ] . Molecules, 2019, 24(17): 3051. DOI: 10.3390/molecule s24173051.

ZHOU S WANG G H QIAO L Age-dependent variations of cancellous bone in response to ovariectomy in C57BL/6J mice Exp Ther Med 2018 15 4 3623 3632 10.3892/etm.2018.5839 ZHOU S, WANG G H, QIAO L, et al . Age-dependent variations of cancellous bone in response to ovariectomy in C57BL/6J mice[J ] . Exp Ther Med, 2018, 15(4): 3623-3632. DOI: 10.3892/etm.2018.5839.

WANG J M HOU X ADEOSUN S A dominant negative ERβ splice variant determines the effectiveness of early or late estrogen therapy after ovariectomy in rats PLoS ONE 2012 7 3 e33493 10.1371/journal.pone.0033493 WANG J M, HOU X, ADEOSUN S, et al . A dominant negative ERβ splice variant determines the effectiveness of early or late estrogen therapy after ovariectomy in rats[J ] . PLoS ONE, 2012, 7(3): e33493. DOI: 10.1371/journal.pone.0033493.

DANIELSEN C C MOSEKILDE L SVENSTRUP B Cortical bone mass, composition, and mechanical properties in female rats in relation to age, long-term ovariectomy, and estrogen substitution Calcif Tissue Int 1993 52 1 26 33 10.1007/BF00675623 DANIELSEN C C, MOSEKILDE L, SVENSTRUP B. Cortical bone mass, composition, and mechanical properties in female rats in relation to age, long-term ovariectomy, and estrogen substitution[J]. Calcif Tissue Int, 1993, 52(1): 26-33. DOI: 10.1007/BF00675623.

CAO J VENTON L SAKATA T Expression of RANKL and OPG correlates with age-related bone loss in male C57BL/6 mice J Bone Miner Res 2003 18 2 270 277 10.1359/jbmr.2003.18.2.270 CAO J, VENTON L, SAKATA T, et al . Expression of RANKL and OPG correlates with age-related bone loss in male C57BL/6 mice[J ] . J Bone Miner Res, 2003, 18(2): 270-277. DOI: 10.1359/jbmr.2003.18.2.270.

BERGMAN R J GAZIT D KAHN A J Age-related changes in osteogenic stem cells in mice J Bone Miner Res 1996 11 5 568 577 10.1002/jbmr.5650110504 BERGMAN R J, GAZIT D, KAHN A J, et al . Age-related changes in osteogenic stem cells in mice[J ] . J Bone Miner Res, 1996, 11(5): 568-577. DOI: 10.1002/jbmr.5650110504.

商敏雌激素受体α及β亚型与绝经后骨质疏松的关系中国骨质疏松杂志 2010 16 4 295 299 10.3969/j.issn.1006-7108.2010.04.016 商敏. 雌激素受体α及β亚型与绝经后骨质疏松的关系[J]. 中国骨质疏松杂志, 2010, 16(4): 295-299. DOI: 10.3969/j.issn.1006-7108.2010.04.016.

陈伟健晋大祥谢炜星 Runx2基因参与骨代谢相关通路的研究进展中国骨质疏松杂志 2018 24 4 557 560 10.3969/j.issn.1006-7108.2018.04.028 陈伟健, 晋大祥, 谢炜星, 等. Runx2基因参与骨代谢相关通路的研究进展[J]. 中国骨质疏松杂志, 2018, 24(4): 557-560. DOI: 10.3969/j.issn.1006-7108.2018.04.028.

周年林鑫陆杨 SIRT1通过β-catenin信号调控干细胞成软骨与成骨分化第三军医大学学报 2020 42 13 1308 1314 10.16016/j.1000-5404.202002213 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=202002213 周年, 林鑫, 陆杨. SIRT1通过β-catenin信号调控干细胞成软骨与成骨分化[J]. 第三军医大学学报, 2020, 42(13): 1308-1314. DOI: 10.16016/j.1000-5404.202002213.

HUANG R L YUAN Y TU J Opposing TNF-α/IL-1β- and BMP-2-activated MAPK signaling pathways converge on Runx2 to regulate BMP-2-induced osteoblastic differentiation Cell Death Dis 2014 5 4 e1187 10.1038/cddis.2014.101 HUANG R L, YUAN Y, TU J, et al . Opposing TNF-α/IL-1β- and BMP-2-activated MAPK signaling pathways converge on Runx2 to regulate BMP-2-induced osteoblastic differentiation[J ] . Cell Death Dis, 2014, 5(4): e1187. DOI: 10.1038/cddis.2014.101.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Role and mechanism of dexmedetomidine in regulating bone metabolism in tail-suspended osteoporotic rats

Cynomorium Songaricum polysaccharide improves osteoporosis in ovariectomized rats

Effects of IGF-1 on osteoporosis in diabetic rats

Influence of the volume of bone cement on the reinforcement of a novel canulated pedicle screw: a biomechanical study in vitro

Percutaneous kyphoplasty through unilateral extrapedicular approach in treating severe osteoporotic vertebral compression fractures

Related Author

WANG Can

ZHANG Xinyu

YAN Zedong

WEN Zhipeng

LIU Ruobing

LIU Pengsen

GUO Yunliang

李晓鸣

Related Institution

Department of Anesthesiology， Henan Provincial Hospital of Traditional Chinese Medicine

Faculty of Biomedical Engineering， Airforce Medical University

⁰