PDE4 inhibitor upregulates PTH-induced osteoclast formation via CRE-mediated COX-2 expression in osteoblasts

Hyojung Park, A. Long Sae Mi No, Jung Min Lee, Ling Chen, Soo Young Lee, Dong Seok Lee, Mijung Yim

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)173-180
Number of pages8
JournalFEBS Letters
Volume584
Issue number1
DOIs
StatePublished - 4 Jan 2010

Keywords

  • COX-2
  • CRE
  • Osteoblast
  • Osteoclast
  • Parathyroid hormone
  • Phosphodiesterase 4
  • RANKL

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