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. Copyright © 2013 John Wiley & Sons, Ltd.