Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 박혜영 | - |
dc.date.accessioned | 2016-08-28T10:08:03Z | - |
dc.date.available | 2016-08-28T10:08:03Z | - |
dc.date.issued | 2012 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.other | OAK-9469 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/223190 | - |
dc.description.abstract | 5-Lipoxygenase (5-LO) catalyzes the formation of two major groups of leukotrienes, leukotriene B4 and cysteinyl leukotrienes (CysLTs), and it has been implicated as a promising drug target to treat various inflammatory diseases. However, its role in osteoclastogenesis has not been investigated. In this study, we used mouse bone marrow-derived macrophages (BMMs) to show that 5-LO inhibitor suppresses RANKL-induced osteoclast formation. Inhibition of 5-LO was associated with impaired activation of multiple signaling events downstream of RANK, including ERK and p38 phosphorylation, and IkB degradation, followed by a decrease in NFATc1 expression. Ectopic overexpression of a constitutively active form of NFATc1 partly rescued the antiosteoclastogenic effect of 5-LO inhibitor. The knockdown of 5-LO in BMMs also resulted in a significant reduction in RANKL-induced osteoclast formation, accompanied by decreased expression of NFATc1. Similar effects were shown with CysLT receptor (CysLTR)1/2 antagonist and small RNA for CysLTR1 in BMMs, indicating the involvement of CysLT and CysLTR1 in 5-LO-mediated osteoclastogenesis. Finally, 5-LO inhibitor suppressed LPS-induced osteoclast formation and bone loss in the in vivo mouse experiments, suggesting a potential therapeutic strategy for treating diseases involving bone destruction. Taken together, the results of this study demonstrate that 5-LO is a key mediator of RANKL-induced osteoclast formation and possibly a novel therapeutic target for boneresorption diseases. Copyright © 2012 by The American Association of Immunologists, Inc. | - |
dc.language | English | - |
dc.title | 5-Lipoxygenase mediates RANKL-induced osteoclast formation via the cysteinyl leukotriene receptor 1 | - |
dc.type | Article | - |
dc.relation.issue | 11 | - |
dc.relation.volume | 189 | - |
dc.relation.index | SCI | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 5284 | - |
dc.relation.lastpage | 5292 | - |
dc.relation.journaltitle | Journal of Immunology | - |
dc.identifier.doi | 10.4049/jimmunol.1003738 | - |
dc.identifier.wosid | WOS:000311287600025 | - |
dc.identifier.scopusid | 2-s2.0-84869826356 | - |
dc.author.google | Lee J.-M. | - |
dc.author.google | Park H. | - |
dc.author.google | Noh A.L.S.M. | - |
dc.author.google | Kang J.-H. | - |
dc.author.google | Chen L. | - |
dc.author.google | Zheng T. | - |
dc.author.google | Lee J. | - |
dc.author.google | Ji S.-Y. | - |
dc.author.google | Jang C.-Y. | - |
dc.author.google | Shin C.S. | - |
dc.author.google | Ha H. | - |
dc.author.google | Lee Z.H. | - |
dc.author.google | Park H.-Y. | - |
dc.author.google | Lee D.-S. | - |
dc.author.google | Yim M. | - |
dc.contributor.scopusid | 박혜영(34972649500;57200273796) | - |
dc.date.modifydate | 20230411110509 | - |