Costunolide inhibits osteoclast differentiation by suppressing c-Fos transcriptional activity.

Yoon-Hee Cheon, Mi Jin Song, Ju-Young Kim, Seong Cheoul Kwak, Ju Ha Park, Chang Hoon Lee, Jeong Joong Kim, Jung Young Kim, Min Kyu Choi, Jaemin Oh, Youn-Chul Kim, Kwon-Ha Yoon, Han Bok Kwak, Myeung Su Lee

Index: Phytother Res. 28(4) , 586-92, (2014)

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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.Copyright © 2013 John Wiley & Sons, Ltd.