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