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This Article Full Text Full Text (PDF) All Versions of this Article: JME-09-0012v1 43/5/197    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hong, S. H H Articles by Mitchell, J. PubMed PubMed Citation Articles by Hong, S. H H Articles by Mitchell, J.

Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Room 4342, Toronto, Ontario, Canada M5S 1A8
¹ Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, Georgia 30033, USA

(Correspondence should be addressed to J Mitchell; Email: jane.mitchell{at}utoronto.ca)

Parathyroid hormone (PTH) binds to its receptor on osteoblasts to regulate gene transcription primarily through the elevation of the second messenger cAMP. A number of genes regulated by PTH in osteoblasts contain GC-rich and Sp-binding sites. Osterix (Osx, Sp7) is a transcription factor required for the differentiation of osteoblasts that can bind to Sp-binding sites on gene promoters and regulate their expression. Here, we report the effect of PTH (1–34) on Osx expression in osteoblastic UMR-106-01 cells and murine calvaria. PTH (1–34) and PTH (1–31) inhibited Osx mRNA and protein expression, and this effect could be mimicked by forskolin, 8-bromo-cAMP, or expression of constitutively active Gs (caGs). Treatment of the cells with PTH (3–34) or the EPAC-selective agonist 8CPT-2Me-cAMP had no effect on Osx mRNA, whereas PTH (7–34) or expression of caGq-stimulated Osx mRNA levels. PTH (1–34) treatment did not require new protein synthesis and did not involve changes in Osx mRNA stability. Osx promoter fragments coupled to a luciferase reporter were inhibited by PTH (1–34) treatment in a similar manner to the inhibition of Osx mRNA and protein. Deletion analysis localized PTH inhibition to two regions flanking the Osx1 start site; –304/–119 and –71/+91. These results demonstrate that prolonged exposure to PTH inhibits Osx expression in osteoblasts through sites on its proximal promoter and this suppression occurs through PTH stimulation of cellular cAMP.