Costunolide inhibits osteoclast differentiation by suppressing c-Fos transcriptional activity.
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.
['Cheon|Yoon-Hee|YH|', 'Song|Mi Jin|MJ|', 'Kim|Ju-Young|JY|', 'Kwak|Seong Cheoul|SC|', 'Park|Ju Ha|JH|', 'Lee|Chang Hoon|CH|', 'Kim|Jeong Joong|JJ|', 'Kim|Jung Young|JY|', 'Choi|Min Kyu|MK|', 'Oh|Jaemin|J|', 'Kim|Youn-Chul|YC|', 'Yoon|Kwon-Ha|KH|', 'Kwak|Han Bok|HB|', 'Lee|Myeung Su|MS|']
D000818:Animals D001854:Bone Marrow Cells D002454:Cell Differentiation D008297:Male D051379:Mice D020928:Mitogen-Activated Protein Kinases D016328:NF-kappa B D050778:NFATC Transcription Factors D010010:Osteoclasts D016760:Proto-Oncogene Proteins c-fos D053245:RANK Ligand D012717:Sesquiterpenes D015398:Signal Transduction D014158:Transcription, Genetic
costunolide osteoclast c-Fos sesquiterpene lactone osteoporosis