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PDE4 inhibitor upregulates PTH‐induced osteoclast formation via CRE‐mediated COX‐2 expression in osteoblasts
Author(s) -
Park Hyojung,
No A Long Sae Mi,
Lee Jung-Min,
Chen Ling,
Lee Soo Young,
Lee Dong-Seok,
Yim Mijung
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.11.043
Subject(s) - parathyroid hormone , rankl , osteoclast , chemistry , medicine , messenger rna , osteoblast , endocrinology , creb , phosphodiesterase , transcription factor , activator (genetics) , biology , in vitro , receptor , gene , calcium , biochemistry , enzyme
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.