5-Lipoxygenase inhibitors suppress RANKL-induced osteoclast formation via NFATc1 expression
- 주제(키워드) 5-Lipoxygenase , Benzoxazole scaffold , formation , Lipopolysaccharide (LPS)-induced osteoclast , NFATc1 , RANKL-induced osteoclast formation
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier Ltd
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000120203
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bmc.2015.09.025
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
5-Lipoxygenase synthesizes leukotrienes from arachidonic acid. We developed three novel 5-LO inhibitors having a benzoxazole scaffold as a potential anti-osteoclastogenics. They significantly suppressed RANKL-induced osteoclast formation in mouse bone marrow-derived macrophages. Furthermore, one compound, K7, inhibited the bone resorptive activity of osteoclasts. The anti-osteoclastogenic effect of K7 was mainly attributable to reduction in the expression of NFATc1, an essential transcription factor for osteoclast differentiation. K7 inhibited osteoclast formation via ERK and p38 MAPK, as well as NF-κB signaling pathways. K7 reduced lipopolysaccharide (LPS)-induced osteoclast formation in vivo, corroborating the in vitro data. Thus, K7 exerted an inhibitory effect on osteoclast formation in vitro and in vivo, properties that make it a potential candidate for the treatment of bone diseases associated with excessive bone resorption. © 2015 Elsevier Ltd. All rights reserved.
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