PDE4 inhibitor upregulates PTH-induced osteoclast formation via CRE-mediated COX-2 expression in osteoblasts.
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.
Park
Hyojung
H
College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
No
A Long Sae Mi
AL
Lee
Jung-Min
JM
Chen
Ling
L
Lee
Soo Young
SY
Lee
Dong-Seok
DS
Yim
Mijung
M
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology*; D010010:Osteoclasts / Q000201:enzymology / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D058988:Phosphodiesterase 4 Inhibitors; D053245:RANK Ligand / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D010281:Parathyroid Hormone; D058988:Phosphodiesterase 4 Inhibitors; D053245:RANK Ligand; D051546:Cyclooxygenase 2; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4