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PDE4 inhibitor upregulates PTH-induced osteoclast formation via CRE-mediated COX-2 expression in osteoblasts
- Authors
- Park, Hyojung; No, A. Long Sae Mi; Lee, Jung-Min; Chen, Ling; Lee, Soo Young; Lee, Dong-Seok; Yim, Mijung
- Issue Date
- 4-Jan-2010
- Publisher
- WILEY
- Keywords
- Parathyroid hormone; Phosphodiesterase 4; RANKL; COX-2; CRE; Osteoblast; Osteoclast
- Citation
- FEBS LETTERS, v.584, no.1, pp 173 - 180
- Pages
- 8
- Journal Title
- FEBS LETTERS
- Volume
- 584
- Number
- 1
- Start Page
- 173
- End Page
- 180
- ISSN
- 0014-5793
1873-3468
- Abstract
- We investigated the interplay between parathyroid hormone (PTH) and phosphodiesterases (PDEs) in osteoblasts. PDE4 negatively regulated PTH-induced cAMP accumulation. PDE4 inhibitor enhanced PTH-induced osteoclast formation and RANKL mRNA expression, which is partially mediated by COX-2 mRNA expression. Two CRE sites in the COX-2 promoter were required for the increase in COX-2 transcription by PDE4 inhibitor, and the expression of a dominant-negative form of CREB abolished COX-2 mRNA expression in response to PDE4 inhibitor or PTH in osteoblasts. Taken together, our data indicate that PDE4 inhibitor promotes PTH-induced osteoclast formation partially via CRE-mediated COX-2 mRNA expression. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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