RT Journal Article
SR Electronic
T1 AB0609 Costunolide inhibits rankl-induced osteoclast differentiation by suppressing rankl-mediated c-fos transcriptional activity.
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP A976
OP A976
DO 10.1136/annrheumdis-2013-eular.2931
VO 72
IS Suppl 3
A1 C.-H. Lee
A1 W.-H. Yoo
A1 Y.-G. Jeong
A1 J.-M. Oh
A1 M.-S. Lee
A1 S.-I. Lee
A1 Y.-H. Cheon
A1 H.-B. Kwak
YR 2013
UL http://ard.bmj.com/content/72/Suppl_3/A976.1.abstract
AB Background Costunolide, a sesquiterpene lactone, exhibits anti-inflammatory and anti-oxidant propertiesand mediates apoptosis. However, its effects and mechanism of action in osteoclasts remains unknown. Objectives We investigated the role of constunolide in RANKL-induced osteoclast differentiation. Methods Osteoclast formation was evaluated in bone marrow cells (BMC) in the presence or absence of constunolide. The expression of c-fos and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of c-fos and NFATc1 protein were assessed by western blot. Also the MAPKs and NF-κB pathways were measured using Western blot analysis. Results we found that costunolide significantly inhibited RANKL-induced BMM differentiation into osteoclasts in a dose-dependent manner without affeting cytotoxicity. Costunolide did not regulate the early signaling pathways of RANKL, including the mitogen activated protein kinase (MAPK) 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. Conclusions Taken together, our results suggest that costunolide inhibited RANKL-induced osteoclast differentiation by suppressing RANKL-mediated c-Fos transcriptional activity. Disclosure of Interest None Declared