title: PDE4 inhibitor suppresses PGE2-induced osteoclast formation via COX-2-mediated p27(KIP1) expression in RAW264.7 cells.
abstract: We investigated the effects of phosphodiesterase 3 (PDE3) and PDE4 inhibitors, which are cAMP degrading enzymes, on prostaglandin E2 (PGE2)-induced osteoclast formation. A PDE4 inhibitor decreased PGE2-induced osteoclast formation, whereas a PDE3 inhibitor did not, possibly due to the lack of PDE3 expression in RAW 264.7 cells. Cell cycle analysis revealed that the PDE4 inhibitor stimulated PGE2-induced p27(KIP1) expression, which leads to increased growth arrest at G0/G1 phase. The PDE4 inhibitor increased cyclooxygenase 2 (COX-2) expression in the presence of PGE2. COX-2 overexpression was associated with growth suppression via p27(KIP1) expression in RAW 264.7 cells. Taken together, our data demonstrate that the PDE4 inhibitor enhances PGE2-induced growth arrest of osteoclast precursors via COX-2-mediated p27(KIP1) expression, which in turn negatively regulates osteoclast formation.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.forename: Hyojung
authors.initials: H
authors.lastname: Park
authors.forename: A Long Sae Mi
authors.initials: AL
authors.lastname: Noh
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
authors.forename: Mijung
authors.initials: M
authors.lastname: Yim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000502:physiology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005434:Flow Cytometry; D007202:Indicators and Reagents; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects*; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: C493961:Cdkn1b protein, mouse; D004396:Coloring Agents; D007202:Indicators and Reagents; D058988:Phosphodiesterase 4 Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; C022616:thiazolyl blue; D015232:Dinoprostone