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Ovariectomy and genes encoding core circadian regulatory proteins in murine bone

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Abstract

Summary

This study investigated the influence of ovarian hormone deficiency on core circadian regulatory protein (CCRP) in the context of bone loss. Our data suggest that ovarian hormone deficiency disrupts diurnal rhythmicity and CCRP expression in bone. Further studies should determine if chronobiology provides a novel therapeutic target for osteoporosis intervention.

Introduction

CCRP synchronize metabolic activities and display an oscillatory expression profile in murine bone. In vitro studies using bone marrow mesenchymal stromal/stem cells have demonstrated that the CCRP is present and can be regulated within osteoblast progenitors. In vivo studies have shown that the CCRP regulates bone mass via leptin/neuroendocrine pathways. The current study used an ovariectomized murine model to test the hypothesis that ovarian hormone deficiency is associated with either an attenuation and/or temporal phase shift of the CCRP oscillatory expression in bone and that these changes are correlated with the onset of osteoporosis.

Methods

Sham-operated controls and ovariectomized female C57BL/6 mice were euthanized at 4-h intervals 2 weeks post-operatively.

Results

Ovariectomy attenuated the oscillatory expression of CCRP mRNAs in the femur and vertebra relative to the controls and reduced the wheel-running activity profile.

Conclusion

Ovarian hormone deficiency modulates the expression profile of the CCRP with potential impact on bone marrow mesenchymal stem cell lineage commitment.

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Acknowledgements

The authors thank Laura Dallam, Susan Newman, Barry Robert DVM, PhD, and the Genomics and Comparative Biology Cores at PBRC and financial support from the Pennington Biomedical Research Foundation (J.M.G., X.W.) and the Clinical Nutrition Research Unit Center Grant #1P30 DK072476 entitled “Nutritional Programming: Environmental and Molecular Interactions” sponsored by NIDDK (A.A.B., J.M.G., G.Y.).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Nutritional Sciences, Oklahoma State University, 423 HES, Stillwater, OK, 74078, USA

    B. J. Smith

  2. Neuropeptides Laboratory, Baton Rouge, LA, USA

    G. M. Sutton & A. A. Butler

  3. Stem Cell Biology Laboratory, Baton Rouge, LA, USA

    X. Wu, G. Yu, B. C. Goh, T. Hebert & J. M. Gimble

  4. Clinical Nutrition Research Unit, Pennington Biomedical Research Center, Baton Rouge, LA, USA

    G. Yu, A. A. Butler & J. M. Gimble

  5. Skeletal Biotechnology Laboratory, Hebrew University–Hadassah Medical Campus, Jerusalem, Israel

    G. Pelled, Z. Gazit & D. Gazit

  6. Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    G. Pelled, Z. Gazit & D. Gazit

Authors
  1. B. J. Smith
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  2. G. M. Sutton
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  3. X. Wu
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  4. G. Yu
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  5. B. C. Goh
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  6. T. Hebert
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  7. G. Pelled
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  8. Z. Gazit
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  9. D. Gazit
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  10. A. A. Butler
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  11. J. M. Gimble
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Corresponding author

Correspondence to B. J. Smith.

Additional information

Smith, Sutton, Wu, Gimble shared equally.

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Smith, B.J., Sutton, G.M., Wu, X. et al. Ovariectomy and genes encoding core circadian regulatory proteins in murine bone. Osteoporos Int 22, 1633–1639 (2011). https://doi.org/10.1007/s00198-010-1325-z

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  • DOI: https://doi.org/10.1007/s00198-010-1325-z

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