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Costunolide Inhibits Osteoclast Differentiation by Suppressing c‐Fos Transcriptional Activity
Author(s) -
Cheon YoonHee,
Song Mi Jin,
Kim JuYoung,
Kwak Seong Cheoul,
Park Ju Ha,
Lee Chang Hoon,
Kim Jeong Joong,
Kim Jung Young,
Choi Min Kyu,
Oh Jaemin,
Kim YounChul,
Yoon KwonHa,
Kwak Han Bok,
Lee Myeung Su
Publication year - 2014
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5034
Subject(s) - rankl , osteoclast , signal transduction , microbiology and biotechnology , nf κb , sesquiterpene lactone , transcription factor , biology , apoptosis , cellular differentiation , chemistry , kinase , biochemistry , in vitro , receptor , activator (genetics) , gene , sesquiterpene , botany
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. Copyright © 2013 John Wiley & Sons, Ltd.