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5-Lipoxygenase Mediates RANKL-Induced Osteoclast Formation via the Cysteinyl Leukotriene Receptor 1
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Jung-Min | - |
dc.contributor.author | Park, Hyojung | - |
dc.contributor.author | Noh, A Long Sae Mi | - |
dc.contributor.author | Kang, Ju-Hee | - |
dc.contributor.author | Chen, Ling | - |
dc.contributor.author | Zheng, Ting | - |
dc.contributor.author | Lee, Juhyun | - |
dc.contributor.author | Ji, Sun-Young | - |
dc.contributor.author | Jang, Chang-Young | - |
dc.contributor.author | Shin, Chan Soo | - |
dc.contributor.author | Ha, Hyunil | - |
dc.contributor.author | Lee, Zang Hee | - |
dc.contributor.author | Park, Hea-Young | - |
dc.contributor.author | Lee, Dong-Seok | - |
dc.contributor.author | Yim, Mijung | - |
dc.creator | 이장희 | - |
dc.date.accessioned | 2013-04-22T04:25:54Z | - |
dc.date.available | 2013-04-22T04:25:54Z | - |
dc.date.issued | 2012-12 | - |
dc.identifier.citation | JOURNAL OF IMMUNOLOGY Vol.189 No.11, pp. 5284-5292 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | https://hdl.handle.net/10371/82233 | - |
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 I kappa B 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 bone-resorption diseases. The Journal of Immunology, 2012, 189: 5284-5292. | en |
dc.language.iso | en | en |
dc.publisher | American Association of Immunologists | en |
dc.subject | 복합학 | en |
dc.title | 5-Lipoxygenase Mediates RANKL-Induced Osteoclast Formation via the Cysteinyl Leukotriene Receptor 1 | en |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 이정민 | - |
dc.contributor.AlternativeAuthor | 박효정 | - |
dc.contributor.AlternativeAuthor | 강주희 | - |
dc.contributor.AlternativeAuthor | 이주현 | - |
dc.contributor.AlternativeAuthor | 지선영 | - |
dc.contributor.AlternativeAuthor | 장창영 | - |
dc.contributor.AlternativeAuthor | 신찬수 | - |
dc.contributor.AlternativeAuthor | 하현일 | - |
dc.contributor.AlternativeAuthor | 이장희 | - |
dc.contributor.AlternativeAuthor | 박혜영 | - |
dc.contributor.AlternativeAuthor | 이동석 | - |
dc.contributor.AlternativeAuthor | 임미정 | - |
dc.identifier.doi | 10.4049/jimmunol.1003738 | - |
dc.description.srnd | OAIID:oai:osos.snu.ac.kr:snu2012-01/102/0000026258/5 | - |
dc.description.srnd | SEQ:5 | - |
dc.description.srnd | PERF_CD:SNU2012-01 | - |
dc.description.srnd | EVAL_ITEM_CD:102 | - |
dc.description.srnd | USER_ID:0000026258 | - |
dc.description.srnd | ADJUST_YN:Y | - |
dc.description.srnd | EMP_ID:A076310 | - |
dc.description.srnd | DEPT_CD:861 | - |
dc.description.srnd | CITE_RATE:5.788 | - |
dc.description.srnd | FILENAME:JI-LOX.pdf | - |
dc.description.srnd | DEPT_NM:치의학과 | - |
dc.description.srnd | EMAIL:zang1959@snu.ac.kr | - |
dc.description.srnd | SCOPUS_YN:Y | - |
dc.description.srnd | CONFIRM:Y | - |
dc.identifier.srnd | 2012-01/102/0000026258/5 | - |
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