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Phosphodiesterase 3 and 4 Negatively Regulate Receptor Activator of Nuclear Factor-kappa B Ligand-Mediated Osteoclast Formation by Prostaglandin E-2

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dc.contributor.authorNoh, A. Long Sae Mi-
dc.contributor.authorYang, Mihye-
dc.contributor.authorLee, Jung-Min-
dc.contributor.authorPark, Hyojung-
dc.contributor.authorLee, Dong-Seok-
dc.contributor.authorYim, Mijung-
dc.date.available2021-02-22T14:16:06Z-
dc.date.created2020-09-03-
dc.date.issued2009-11-
dc.identifier.issn0918-6158-
dc.identifier.urihttps://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13660-
dc.description.abstractProstaglandin E-2 (PGE(2)) stimulates osteoclast formation by increasing receptor activator of nuclear factor (NF)-kappa B ligand (RANKL) mRNA expression via cAMP-protein kinase A (PKA) pathways in osteoblasts. Since phosphodiesterases (PDEs) balance the concentration of intracellular cAMP stimulated by PGE(2), we investigated the role of PDEs in PGE(2)-mediated osteoclast formation using various cAMP-specific PDEs inhibitors. In the presence of PGE(2), PDE3 and 4 inhibitors were shown to dose-dependently increase the osteoclast formation in cocultures of mouse bone marrow cells and calvarial osteoblasts. In agreement with this finding, they stimulated PGE(2)-induced cAMP production followed by increased RANKL mRNA expression in osteoblasts, suggesting that PDE3 and 4 negatively regulate PGE(2)-mediated RANKL expression in osteoblasts. RT-PCR analysis revealed that PDE3A, 3B, 4A, 4B and 4D are expressed in osteoblasts. The PDE8 inhibitor did not increase osteoclast formation, although it stimulated PGE(2)-induced RANKL mRNA expression in osteoblasts. The four subtypes of PGE receptors are designated EP1, EP2, EP3 and EP4, PDE3 and 4 inhibitors were found to increase EP1/3, EP4 and/or EP2 agonist-stimulated RANKL expression, indicating that PDE3 and PDE4 negatively regulate PGE(2)-induced RANKL mRNA expression through four EPs. Taken together, these data suggest that PDE3 and PDE4 could have important pharmacological and clinical implications in hone-related diseases.-
dc.language영어-
dc.language.isoen-
dc.publisherPHARMACEUTICAL SOC JAPAN-
dc.subjectNECROSIS-FACTOR RECEPTOR-
dc.subjectBONE-RESORPTION-
dc.subjectOSTEOBLASTIC CELLS-
dc.subjectPROTEIN-KINASE-
dc.subjectDIFFERENTIATION-
dc.subjectTRANCE/RANKL-
dc.subjectINVOLVEMENT-
dc.subjectEXPRESSION-
dc.subjectINHIBITOR-
dc.subjectAGONISTS-
dc.titlePhosphodiesterase 3 and 4 Negatively Regulate Receptor Activator of Nuclear Factor-kappa B Ligand-Mediated Osteoclast Formation by Prostaglandin E-2-
dc.typeArticle-
dc.contributor.affiliatedAuthorYim, Mijung-
dc.identifier.doi10.1248/bpb.32.1844-
dc.identifier.scopusid2-s2.0-70350708143-
dc.identifier.wosid000271252900006-
dc.identifier.bibliographicCitationBIOLOGICAL & PHARMACEUTICAL BULLETIN, v.32, no.11, pp.1844 - 1848-
dc.relation.isPartOfBIOLOGICAL & PHARMACEUTICAL BULLETIN-
dc.citation.titleBIOLOGICAL & PHARMACEUTICAL BULLETIN-
dc.citation.volume32-
dc.citation.number11-
dc.citation.startPage1844-
dc.citation.endPage1848-
dc.type.rimsART-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalResearchAreaPharmacology & Pharmacy-
dc.relation.journalWebOfScienceCategoryPharmacology & Pharmacy-
dc.subject.keywordPlusNECROSIS-FACTOR RECEPTOR-
dc.subject.keywordPlusBONE-RESORPTION-
dc.subject.keywordPlusOSTEOBLASTIC CELLS-
dc.subject.keywordPlusPROTEIN-KINASE-
dc.subject.keywordPlusDIFFERENTIATION-
dc.subject.keywordPlusTRANCE/RANKL-
dc.subject.keywordPlusINVOLVEMENT-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusINHIBITOR-
dc.subject.keywordPlusAGONISTS-
dc.subject.keywordAuthorprostaglandin E-2-
dc.subject.keywordAuthorphosphodiesterase-
dc.subject.keywordAuthorosteoblast, osteoclast-
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