title: Costunolide inhibits osteoclast differentiation by suppressing c-Fos transcriptional activity.
abstract: Costunolide, a sesquiterpene lactone, exhibits anti-inflammatory and anti-oxidant properties and mediates apoptosis. However, its effects and mechanism of action in osteoclasts remain unknown. Herein, we found that costunolide significantly inhibited RANKL-induced BMM differentiation into osteoclasts in a dose-dependent manner without affecting cytotoxicity. Costunolide did not regulate the early signaling pathways of RANKL, including the mitogen-activated protein kinase and NF-κB pathways. However, costunolide suppressed nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) expression via inhibition of c-Fos transcriptional activity without affecting RANKL-induced c-Fos expression. The inhibitory effects of costunolide were rescued by overexpression of constitutively active (CA)-NFATc1. Taken together, our results suggest that costunolide inhibited RANKL-induced osteoclast differentiation by suppressing RANKL-mediated c-Fos transcriptional activity.
authors.affiliation: Department of Anatomy, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk, 570-749, Korea.
authors.forename: Yoon-Hee
authors.initials: YH
authors.lastname: Cheon
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Song
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Seong Cheoul
authors.initials: SC
authors.lastname: Kwak
authors.forename: Ju Ha
authors.initials: JH
authors.lastname: Park
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Jeong Joong
authors.initials: JJ
authors.lastname: Kim
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Min Kyu
authors.initials: MK
authors.lastname: Choi
authors.forename: Jaemin
authors.initials: J
authors.lastname: Oh
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Kwon-Ha
authors.initials: KH
authors.lastname: Yoon
authors.forename: Han Bok
authors.initials: HB
authors.lastname: Kwak
authors.forename: Myeung Su
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D007783:Lactones
chemical_list: D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D012717:Sesquiterpenes; C002602:costunolide; D007783:Lactones
keywords: c-Fos; costunolide; osteoclast; osteoporosis; sesquiterpene lactone