Phosphodiesterase 4 inhibitor regulates the TRANCE/OPG ratio via COX-2 expression in a manner similar to PTH in osteoblasts

Hyojung Park; Soo Young Lee; Dong Seok Lee; Mijung Yim

doi:10.1016/j.bbrc.2006.12.174

Phosphodiesterase 4 inhibitor regulates the TRANCE/OPG ratio via COX-2 expression in a manner similar to PTH in osteoblasts

Hyojung Park, Soo Young Lee, Dong Seok Lee, Mijung Yim

Department of Life Science

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Phosphodiesterase 4 (PDE4) inhibitors stimulate osteoclast formation by increasing the TRANCE/OPG mRNA ratio via cAMP-mediated pathways in a manner similar to parathyroid hormone (PTH) in osteoblasts. We investigated the role of cyclooxygenase-2 (COX-2) in osteoclast formation induced by the PDE4 inhibitor rolipram. Rolipram induced COX-2 expression in mRNA and protein levels, followed by increased prostaglandin E₂ production in osteoblasts. PKA, ERK, and p38 MAPK pathways regulate COX-2 mRNA expression induced by rolipram, in which PKA is a central regulator of the ERK and p38 MAPK pathways. A COX-2 inhibitor reversed the up-regulation of the TRANCE/OPG mRNA ratio induced by rolipram in osteoblasts, resulting in decreased osteoclast formation. These data suggest that COX-2 mediates rolipram induced osteoclast formation by regulating the TRANCE/OPG mRNA ratio in osteoblasts. Furthermore, the effects of the PDE4 inhibitor on osteoblasts were very similar to those of PTH, indicating that the PDE4 inhibitor largely shares the biological actions of PTH in osteoblasts.

Original language	English
Pages (from-to)	178-183
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	354
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2006.12.174
State	Published - 2 Mar 2007

Bibliographical note

Funding Information:
This work was supported by R01-2005-000-10305-0 from the Basic Research Program of the Korea Science and Engineering Foundation, and Korea Research Foundation Grant funded by Korea Government (MOEHRD) (KRF-2005-003E00316).

Keywords

COX-2
OPG
Osteoblast
Osteoclast
Parathyroid hormone
Phosphodiesterase 4
TRANCE

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title = "Phosphodiesterase 4 inhibitor regulates the TRANCE/OPG ratio via COX-2 expression in a manner similar to PTH in osteoblasts",

abstract = "Phosphodiesterase 4 (PDE4) inhibitors stimulate osteoclast formation by increasing the TRANCE/OPG mRNA ratio via cAMP-mediated pathways in a manner similar to parathyroid hormone (PTH) in osteoblasts. We investigated the role of cyclooxygenase-2 (COX-2) in osteoclast formation induced by the PDE4 inhibitor rolipram. Rolipram induced COX-2 expression in mRNA and protein levels, followed by increased prostaglandin E2 production in osteoblasts. PKA, ERK, and p38 MAPK pathways regulate COX-2 mRNA expression induced by rolipram, in which PKA is a central regulator of the ERK and p38 MAPK pathways. A COX-2 inhibitor reversed the up-regulation of the TRANCE/OPG mRNA ratio induced by rolipram in osteoblasts, resulting in decreased osteoclast formation. These data suggest that COX-2 mediates rolipram induced osteoclast formation by regulating the TRANCE/OPG mRNA ratio in osteoblasts. Furthermore, the effects of the PDE4 inhibitor on osteoblasts were very similar to those of PTH, indicating that the PDE4 inhibitor largely shares the biological actions of PTH in osteoblasts.",

keywords = "COX-2, OPG, Osteoblast, Osteoclast, Parathyroid hormone, Phosphodiesterase 4, TRANCE",

author = "Hyojung Park and {Young Lee}, Soo and Lee, {Dong Seok} and Mijung Yim",

note = "Funding Information: This work was supported by R01-2005-000-10305-0 from the Basic Research Program of the Korea Science and Engineering Foundation, and Korea Research Foundation Grant funded by Korea Government (MOEHRD) (KRF-2005-003E00316). ",

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AU - Park, Hyojung

AU - Young Lee, Soo

AU - Lee, Dong Seok

AU - Yim, Mijung

N1 - Funding Information: This work was supported by R01-2005-000-10305-0 from the Basic Research Program of the Korea Science and Engineering Foundation, and Korea Research Foundation Grant funded by Korea Government (MOEHRD) (KRF-2005-003E00316).

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N2 - Phosphodiesterase 4 (PDE4) inhibitors stimulate osteoclast formation by increasing the TRANCE/OPG mRNA ratio via cAMP-mediated pathways in a manner similar to parathyroid hormone (PTH) in osteoblasts. We investigated the role of cyclooxygenase-2 (COX-2) in osteoclast formation induced by the PDE4 inhibitor rolipram. Rolipram induced COX-2 expression in mRNA and protein levels, followed by increased prostaglandin E2 production in osteoblasts. PKA, ERK, and p38 MAPK pathways regulate COX-2 mRNA expression induced by rolipram, in which PKA is a central regulator of the ERK and p38 MAPK pathways. A COX-2 inhibitor reversed the up-regulation of the TRANCE/OPG mRNA ratio induced by rolipram in osteoblasts, resulting in decreased osteoclast formation. These data suggest that COX-2 mediates rolipram induced osteoclast formation by regulating the TRANCE/OPG mRNA ratio in osteoblasts. Furthermore, the effects of the PDE4 inhibitor on osteoblasts were very similar to those of PTH, indicating that the PDE4 inhibitor largely shares the biological actions of PTH in osteoblasts.

AB - Phosphodiesterase 4 (PDE4) inhibitors stimulate osteoclast formation by increasing the TRANCE/OPG mRNA ratio via cAMP-mediated pathways in a manner similar to parathyroid hormone (PTH) in osteoblasts. We investigated the role of cyclooxygenase-2 (COX-2) in osteoclast formation induced by the PDE4 inhibitor rolipram. Rolipram induced COX-2 expression in mRNA and protein levels, followed by increased prostaglandin E2 production in osteoblasts. PKA, ERK, and p38 MAPK pathways regulate COX-2 mRNA expression induced by rolipram, in which PKA is a central regulator of the ERK and p38 MAPK pathways. A COX-2 inhibitor reversed the up-regulation of the TRANCE/OPG mRNA ratio induced by rolipram in osteoblasts, resulting in decreased osteoclast formation. These data suggest that COX-2 mediates rolipram induced osteoclast formation by regulating the TRANCE/OPG mRNA ratio in osteoblasts. Furthermore, the effects of the PDE4 inhibitor on osteoblasts were very similar to those of PTH, indicating that the PDE4 inhibitor largely shares the biological actions of PTH in osteoblasts.

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Phosphodiesterase 4 inhibitor regulates the TRANCE/OPG ratio via COX-2 expression in a manner similar to PTH in osteoblasts

Abstract

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Keywords

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