TY - JOUR 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 SP - A976 LP - A976 DO - 10.1136/annrheumdis-2013-eular.2931 VL - 72 IS - Suppl 3 AU - C.-H. Lee AU - W.-H. Yoo AU - Y.-G. Jeong AU - J.-M. Oh AU - M.-S. Lee AU - S.-I. Lee AU - Y.-H. Cheon AU - H.-B. Kwak Y1 - 2013/06/01 UR - http://ard.bmj.com/content/72/Suppl_3/A976.1.abstract N2 - 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 ER -