Document Detail


Changes in bone sclerostin levels in mice after ovariectomy vary independently of changes in serum sclerostin levels.
MedLine Citation:
PMID:  23044658     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Sandra Jastrzebski; Judith Kalinowski; Marina Stolina; Faryal Mirza; Elena Torreggiani; Ivo Kalajzic; Hee Yeon Won; Sun-Kyeong Lee; Joseph Lorenzo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  28     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-18     Completed Date:  2013-08-29     Revised Date:  2014-03-09    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  618-26     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Society for Bone and Mineral Research.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Enzyme-Linked Immunosorbent Assay
Female
Glycoproteins / blood,  genetics,  metabolism*
Mice
Mice, Inbred C57BL
Ovariectomy*
RNA, Messenger / metabolism
Tomography, X-Ray Computed
Grant Support
ID/Acronym/Agency:
AR0488714/AR/NIAMS NIH HHS; AR055143/AR/NIAMS NIH HHS; AR059315/AR/NIAMS NIH HHS; R01 AR048714/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Glycoproteins; 0/RNA, Messenger; 0/Sost protein, mouse
Comments/Corrections

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