View : 20 Download: 0
5-Lipoxygenase mediates RANKL-induced osteoclast formation via the cysteinyl leukotriene receptor 1
- 5-Lipoxygenase mediates RANKL-induced osteoclast formation via the cysteinyl leukotriene receptor 1
- Lee J.-M.; Park H.; Noh A.L.S.M.; Kang J.-H.; Chen L.; Zheng T.; Lee J.; Ji S.-Y.; Jang C.-Y.; Shin C.S.; Ha H.; Lee Z.H.; Park H.-Y.; Lee D.-S.; Yim M.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Journal of Immunology
- vol. 189, no. 11, pp. 5284 - 5292
- SCI; SCIE; SCOPUS
- 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.
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.