title: Changes in bone sclerostin levels in mice after ovariectomy vary independently of changes in serum sclerostin levels.
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.
authors.affiliation: Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030-5456, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jastrzebski
authors.forename: Judith
authors.initials: J
authors.lastname: Kalinowski
authors.forename: Marina
authors.initials: M
authors.lastname: Stolina
authors.forename: Faryal
authors.initials: F
authors.lastname: Mirza
authors.forename: Elena
authors.initials: E
authors.lastname: Torreggiani
authors.forename: Ivo
authors.initials: I
authors.lastname: Kalajzic
authors.forename: Hee Yeon
authors.initials: HY
authors.lastname: Won
authors.forename: Sun-Kyeong
authors.initials: SK
authors.lastname: Lee
authors.forename: Joseph
authors.initials: J
authors.lastname: Lorenzo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006023:Glycoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C486030:Sost protein, mouse; D000089703:Fibroblast Growth Factor-23