Changes in bone sclerostin levels in mice after ovariectomy vary independently of changes in serum sclerostin levels

Sandra Jastrzebski, Judith Kalinowski, Marina Stolina, Faryal Mirza, Elena Torreggiani, Ivo Kalajzic, Hee Yeon Won, Sun Kyeong Lee, Joseph Lorenzo

Research output: Contribution to journalArticle

Abstract

We examined the effects that ovariectomy had on sclerostin mRNA and protein levels in the bones of 8-week-old mice that were either sham-operated (SHAM) or ovariectomized (OVX) and then euthanized 3 or 6 weeks later. In this model, bone loss occurred between 3 and 5 weeks postsurgery. In calvaria, ovariectomy significantly decreased sclerostin mRNA levels at 6 weeks postsurgery (by 52%) but had no significant effect at 3 weeks. In contrast, sclerostin mRNA levels were significantly lower in OVX femurs at 3 weeks postsurgery (by 53%) but equal to that of SHAM at 6 weeks. The effects of ovariectomy on sclerostin were not a global response of osteocytes because they were not mimicked by changes in the mRNA levels for two other relatively osteocyte-specific genes: DMP-1 and FGF-23. Sclerostin protein decreased by 83% and 60%, at 3 and 6 weeks postsurgery in calvaria, respectively, and by 38% in lumbar vertebrae at 6 weeks. We also detected decreases in sclerostin by immunohistochemistry in cortical osteocytes of the humerus at 3 weeks postsurgery. However, there were no significant effects of ovariectomy on sclerostin protein in femurs or on serum sclerostin at 3 and 6 weeks postsurgery. These results demonstrate that ovariectomy has variable effects on sclerostin mRNA and protein in mice, which are dependent on the bones examined and the time after surgery. Given the discrepancy between the effects of ovariectomy on serum sclerostin levels and sclerostin mRNA and protein levels in various bones, these results argue that, at least in mice, serum sclerostin levels may not accurately reflect changes in the local production of sclerostin in bones. Additional studies are needed to evaluate whether this is also the case in humans.

Original languageEnglish
Pages (from-to)618-626
Number of pages9
JournalJournal of Bone and Mineral Research
Volume28
Issue number3
DOIs
Publication statusPublished - Mar 2013

Keywords

  • BONE
  • OSTEOCYTE
  • OVARIECTOMY
  • SCLEROSTIN
  • SERUM

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

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  • Cite this

    Jastrzebski, S., Kalinowski, J., Stolina, M., Mirza, F., Torreggiani, E., Kalajzic, I., Won, H. Y., Lee, S. K., & Lorenzo, J. (2013). Changes in bone sclerostin levels in mice after ovariectomy vary independently of changes in serum sclerostin levels. Journal of Bone and Mineral Research, 28(3), 618-626. https://doi.org/10.1002/jbmr.1773