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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis

  • Kim, Ju-Young (Imaging Science-based Lung and Bone Diseases Research Center,) ;
  • Cheon, Yoon-Hee (Department of Anatomy, Wonkwang University School of Medicine) ;
  • Yoon, Kwon-Ha (Imaging Science-based Lung and Bone Diseases Research Center,) ;
  • Lee, Myeung Su (Imaging Science-based Lung and Bone Diseases Research Center,) ;
  • Oh, Jaemin (Imaging Science-based Lung and Bone Diseases Research Center,)
  • Received : 2013.09.12
  • Accepted : 2013.11.28
  • Published : 2014.08.31
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Abstract

Parthenolide, a natural product derived from Feverfew, prevents septic shock and inflammation. We aimed to identify the effects of parthenolide on the RANKL (receptor activator of $NF-{\kappa}B$ ligand)-induced differentiation and bone resorbing activity of osteoclasts. In this study, parthenolide dose-dependently inhibited RANKL-mediated osteoclast differentiation in BMMs, without any evidence of cytotoxicity and the phosphorylation of p38, ERK, and $I{\kappa}B$, as well as $I{\kappa}B$ degradation by RANKL treatment. Parthenolide suppressed the expression of NFATc1, OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treated BMMs. Furthermore, parthenolide down-regulated the stability of c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed the inhibitory effect of parthenolide on RANKL-mediated osteoclast differentiation. Parthenolide also inhibited the bone resorbing activity of mature osteoclasts. Parthenolide inhibits the differentiation and bone-resolving activity of osteoclast by RANKL, suggesting its potential therapeutic value for bone destructive disorders associated with osteoclast-mediated bone resorption.

Keywords

References

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