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

doi:10.1016/j.febslet.2009.11.043

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

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14 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 language	English
Pages (from-to)	173-180
Number of pages	8
Journal	FEBS Letters
Volume	584
Issue number	1
DOIs	https://doi.org/10.1016/j.febslet.2009.11.043
State	Published - 4 Jan 2010

Keywords

COX-2
CRE
Osteoblast
Osteoclast
Parathyroid hormone
Phosphodiesterase 4
RANKL

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10.1016/j.febslet.2009.11.043

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

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.",

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T1 - PDE4 inhibitor upregulates PTH-induced osteoclast formation via CRE-mediated COX-2 expression in osteoblasts

AU - Park, Hyojung

AU - No, A. Long Sae Mi

AU - Lee, Jung Min

AU - Chen, Ling

AU - Lee, Soo Young

AU - Lee, Dong Seok

AU - Yim, Mijung

PY - 2010/1/4

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AB - 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.

KW - COX-2

KW - CRE

KW - Osteoblast

KW - Osteoclast

KW - Parathyroid hormone

KW - Phosphodiesterase 4

KW - RANKL

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

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