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Deletion of estrogen receptor beta accelerates early stage of bone healing in a mouse osteotomy model

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Abstract

Summary

This study examined the role of estrogen receptor (ER) beta during mouse femoral fracture healing by employing ER knockout (KO) mice. The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification.

Introduction

This study was conducted to examine the role of ER beta during fracture healing.

Methods

Female ERbeta knockout (KO) mice (18 weeks old) and age-matched female wild-type (WT) mice underwent open osteotomy on the right femur. They were sacrificed at 1, 2, 4 and 6 weeks post-fracture. The sera and callus samples were subjected to the following analyses: micro-computed tomography (CT)-based angiography, micro-CT evaluation, histological examination, histomorphometry examination, real-time polymerase chain reaction (PCR) analysis, biochemical marker, and mechanical testing.

Results

Micro-CT-based angiography showed that the total vessel volume at the fracture site was larger in the KO group than the WT group at 1 and 2 weeks post-fracture. Micro-CT analysis revealed that the callus volume was significantly higher in the KO group from week 2 to week 4 post-fracture when compared with the WT group consistent with the histological data. Analysis of biochemical markers indicated that circulating P1NP levels in the KO mice were significantly higher than in the WT mice from week 2 to week 4 and that temporal expression of circulating C-terminal telopeptide of type I collagen (CTX) levels was also higher in the KO mice than in the WT mice. These results were consistent with quantitative real-time PCR analysis. The ultimate load, stiffness, and energy to failure were significantly higher in the KO mice than in the WT mice at week 4.

Conclusions

The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification, but not by the end of healing. Blockade of ERbeta can be considered as another therapeutic strategy for osteoporotic fracture and non-union fracture.

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Abbreviations

ER:

Estrogen receptor

KO:

Knockout

Micro-CT:

Micro-computed tomography

WT:

Wild-type

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Acknowledgments

This study was supported by AO Research Grant (S-08-74Z) and CUHK Direct Grant (2008.1.063). We also thank Mr. Wang Yu-Gang for his support in animal care.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Shatin, Hong Kong, China

    Y.-X. He, Z. Liu, X.-H. Pan, T. Tang, B.-S. Guo, L.-Z. Zheng, X.-H. Xie, X.-L. Wang, G. Li, L.-K. Hung, L. Qin & G. Zhang

  2. Department of Orthopedics, Shenzhen People’s Hospital, Medical College of Ji Nan University, 518020, Shenzhen, China

    X.-H. Pan

  3. Translational Medicine Research and Development Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, a branch of the Chinese Academy of Science, 518055, Shenzhen, China

    X.-L. Wang & L. Qin

  4. Lee Hysan Clinical Research Laboratory, The Chinese University of Hong Kong, Shatin, Hong Kong, China

    K.-M. Lee

  5. Department of Orthopedics, Peking University First Hospital, 100034, Beijing, China

    Y.-P. Cao

  6. Department of Orthopaedics, Warren Alpert Medical School of Brown University, Providence, RI, USA

    L. Wei

  7. Department of Orthopaedics, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    L. Wei

  8. Department of Orthopedics, Shenzhen Second People’s Hospital, Futian, 518035, Shenzhen, China

    Y. Chen

  9. School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China

    Z.-J. Yang

Authors
  1. Y.-X. He
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  2. Z. Liu
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  3. X.-H. Pan
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  4. T. Tang
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  5. B.-S. Guo
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  6. L.-Z. Zheng
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  7. X.-H. Xie
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  8. X.-L. Wang
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  9. K.-M. Lee
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  10. G. Li
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  11. Y.-P. Cao
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  12. L. Wei
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  13. Y. Chen
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  14. Z.-J. Yang
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  15. L.-K. Hung
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  16. L. Qin
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  17. G. Zhang
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Corresponding authors

Correspondence to L. Qin or G. Zhang.

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He, YX., Liu, Z., Pan, XH. et al. Deletion of estrogen receptor beta accelerates early stage of bone healing in a mouse osteotomy model. Osteoporos Int 23, 377–389 (2012). https://doi.org/10.1007/s00198-011-1812-x

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  • DOI: https://doi.org/10.1007/s00198-011-1812-x

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