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Skeletal changes during lactation and after weaning in osteocyte-specific sclerostin overexpressed mice

  • Su Jin Lee
  • Sun Yong Song
  • Yumie RheeEmail author
Original Article
  • 17 Downloads

Abstract

Introduction

Lactation inevitably leads to a state of rapid bone loss; however, maternal bone undergoes rapid remineralization after weaning. Sclerostin, encoded by the gene SOST, is exclusively secreted from osteocytes and plays important roles in bone remodeling. However, there are few studies about the effect of sclerostin during lactation and weaning on bone microstructures. Therefore, we conducted the study to demonstrate any possible association of sclerostin with bone metabolism and skeletal changes during lactation and after weaning.

Materials and methods

We analyzed bone mineral density (BMD) by dual-energy X-ray absorptiometry at the spine and femur, bone microstructure by micro-computed tomography (μCT) at the distal and mid-shaft of the femur and biochemical markers such as sclerostin and bone turnover markers at 1 week and 3 weeks of lactation and 2 weeks post-weaning in osteocyte-specific sclerostin-overexpressed transgenic mice, and compared them with wild type.

Results

Lactation significantly resulted in decreased spine and femur BMD at day 7 and day 21 of breastfeeding; specifically, cortical microstructure (cross-sectional thickness and cross-sectional area) at the mid-shaft of the femur had significantly deteriorated. At day 14 after weaning, femur BMD and cortical microstructure at the mid-shaft of the femur in both the wild and DMP-SOST mice had incompletely recovered; however, spine BMD and trabecular microstructures at the distal femur recovered in wild type mice.

Conclusions

Sclerostin, secreted by osteocytes, played a role in bone loss during lactation and also in the recovery of trabecular bone compartment by activating bone formation after weaning.

Keywords

Sclerostin Lactation Weaning Bone Microstructure 

Notes

Acknowledgements

This study was funded by the Research Grant from the Department of Internal Medicine, Yonsei University College of Medicine (No. 6-2014-0034). We thank Sung Hwan Moon (Yonsei University), Sahng Wook Park (Yonsei University), Jong In Yuk (Yonsei University), Kyoung Min Kim (Seoul National University Bundang Hospital) for critical comments of the article. We also thank Teresita Bellido (Indiana University school of Medicine) for providing the DMP-SOST mice. We also thank Dae In Kim (Librarian, Yonsei University Medical Library) for his assistance in providing formatting the script.

Author contributions

SJL, SYS, and YR designed the study and generated the hypothesis. SJL and SYS collected the data. SJL analyzed the data and drafted the manuscript. SJL, SYS and YR reviewed the draft and finalized the manuscript.

Compliance with ethical standards

Conflict of interest

All authors state that they have no conflicts of interest.

Ethical approval

All these animal studies were reviewed and approved by the institutional animal care center of department of laboratory animal resources, Yonsei Biomedical Research Institute, Yonsei University College of Medicine (No. 2014-0050-1).

Informed consent

No informed consent was necessary for this study.

Supplementary material

774_2019_1044_MOESM1_ESM.pdf (194 kb)
Supplementary material 1 (PDF 193 kb) Supplement Fig. 1. 3D reconstruction of distal and mid-shaft femur during lactation and weaning period
774_2019_1044_MOESM2_ESM.pptx (103 kb)
Supplementary material 2 (PPTX 102 kb) Supplement Fig. 2. Comparisons of biochemical markers such as sclerostin and bone turnover markers at 1 week and 3 weeks of lactation and 2 weeks post-weaning in wild and DMP-SOST transgenic mice according to lactation WT: wild type, TG: DMP-SOST transgenic mice, P1NP: amino-terminal propeptide of type 1 procollagen, CTX: cross-linked C-telopeptide, *, p-value < 0.05 by t-test. The amino-terminal propeptide of type 1 procollagen (P1NP) (IDS, Boldon, U.K), cross-linked C-telopeptide (CTX)
774_2019_1044_MOESM3_ESM.docx (16 kb)
Supplementary material 3 (DOCX 16 kb)

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Copyright information

© The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Internal Medicine, Severance Hospital, Endocrine Research InstituteYonsei University College of MedicineSeoulSouth Korea
  2. 2.Department of Preventive MedicineYonsei University College of MedicineSeoulSouth Korea

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