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AB0609 Costunolide inhibits rankl-induced osteoclast differentiation by suppressing rankl-mediated c-fos transcriptional activity.
  1. C.-H. Lee1,
  2. W.-H. Yoo2,
  3. Y.-G. Jeong3,
  4. J.-M. Oh4,
  5. M.-S. Lee1,
  6. S.-I. Lee5,
  7. Y.-H. Cheon5,
  8. H.-B. Kwak4
  1. 1Department of Internal Medicine, Wonkwang University Hospital, Iksan
  2. 2Department of Internal Medicine, Chonbuk National University Hospital, Jeonju
  3. 3Department of Internal Medicine, Fatima Hospital, Changwon
  4. 4Department of Anatomy, School of Medicine, Wonkwang University, Iksan
  5. 5Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea, Republic Of

Abstract

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

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