Journal
FEBS LETTERS
Volume 585, Issue 15, Pages 2450-2454Publisher
WILEY
DOI: 10.1016/j.febslet.2011.06.019
Keywords
Sclerostin; PGE2 signaling; Mechanical strain; Osteoporosis
Funding
- Wellcome Trust
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Sclerostin is a potent inhibitor of bone formation which is down-regulated by mechanical loading. To investigate the mechanisms involved we subjected Saos2 human osteoblastic cells to short periods of dynamic strain and used quantitative reverse transcriptase polymerase chain reaction to compare their responses to unstrained controls. Strain-induced Sost down-regulation was recapitulated by cyclo-oxygenase-2-mediated PGE2, acting through the EP4 receptor, whereas strain-related up-regulation of osteocalcin was mediated by the EP2 receptor. Strain-related Sost regulation required extracellular signal-regulated kinase signaling, whereas osteocalcin required protein kinase C. These findings indicate early divergence in the signaling pathways stimulated by strain and establish PGE2/EP4 as the pathway used by strain to regulate Sost expression. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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