PDE4 inhibitor suppresses PGE(2)-induced osteoclast formation via COX-2-mediated p27(KIP1) expression in RAW264.7 cells
- Authors
- Chen, Ling; Zheng, Ting; Park, Hyojung; Noh, A. Long Sae Mi; Lee, Jung-Min; Lee, Dong-Seok; Yim, Mijung
- Issue Date
- Mar-2011
- Publisher
- GOVI-VERLAG PHARMAZEUTISCHER VERLAG GMBH
- Citation
- PHARMAZIE, v.66, no.3, pp 201 - 206
- Pages
- 6
- Journal Title
- PHARMAZIE
- Volume
- 66
- Number
- 3
- Start Page
- 201
- End Page
- 206
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/12637
- DOI
- 10.1691/ph.2011.0747
- ISSN
- 0031-7144
- Abstract
- We investigated the effects of phosphodiesterase 3 (PDE3) and PDE4 inhibitors, which are cAMP degrading enzymes, on prostaglandin E-2 (PGE(2))-induced osteoclast formation. A PDE4 inhibitor decreased PGE(2)-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 PGE(2)-induced p27(KIP1) expression, which leads to increased growth arrest at G(0)/G(1) phase. The PDE4 inhibitor increased cyclooxygenase 2 (COX-2) expression in the presence of PGE(2). 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 PGE(2)-induced growth arrest of osteoclast precursors via COX-2-mediated p27(KIP1) expression, which in turn negatively regulates osteoclast formation.
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