PDE4 inhibitor suppresses PGE2 -induced osteoclast formation via COX-2-mediated p27KIP1 expression in RAW264.7 cells
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 p27KIP1 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 p27KIP1 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 p27KIP1 expression, which in turn negatively regulates osteoclast formation.
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Document Type: Research Article
Publication date: 01 March 2011
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