5-Lipoxygenase inhibitors suppress RANKL-induced osteoclast formation via NFATc1 expression

Ju Hee Kang, Zheng Ting, Mi Ran Moon, Jung Seon Sim, Jung Min Lee, Kyung Eun Doh, Sunhye Hong, Minghua Cui, Sun Choi, Hyeun Wook Chang, Hea Young Park Choo, Mijung Yim

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)7069-7078
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number21
DOIs
StatePublished - 1 Nov 2015

Keywords

  • 5-Lipoxygenase
  • Benzoxazole scaffold
  • formation
  • Lipopolysaccharide (LPS)-induced osteoclast
  • NFATc1
  • RANKL-induced osteoclast formation

Fingerprint

Dive into the research topics of '5-Lipoxygenase inhibitors suppress RANKL-induced osteoclast formation via NFATc1 expression'. Together they form a unique fingerprint.

Cite this