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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cyclic AMP Response Element-Binding Protein / biosynthesis
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
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Cyclooxygenase 2 / biosynthesis*
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Cyclooxygenase 2 / genetics
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Humans
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Mice
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Osteoblasts / drug effects
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Osteoblasts / enzymology*
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Osteoclasts / enzymology
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Osteoclasts / physiology*
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Parathyroid Hormone / pharmacology*
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Phosphodiesterase 4 Inhibitors*
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RANK Ligand / metabolism
Substances
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Cyclic AMP Response Element-Binding Protein
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Parathyroid Hormone
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Phosphodiesterase 4 Inhibitors
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RANK Ligand
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Cyclooxygenase 2
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Cyclic Nucleotide Phosphodiesterases, Type 4