Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis
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Parthenolide, a natural product derived from Feverfew, preventsseptic shock and inflammation. We aimed to identify the effectsof parthenolide on the RANKL (receptor activator of NF-κBligand)-induced differentiation and bone resorbing activity ofosteoclasts. In this study, parthenolide dose-dependentlyinhibited RANKL-mediated osteoclast differentiation in BMMs,without any evidence of cytotoxicity and the phosphorylation ofp38, ERK, and IκB, as well as IκB degradation by RANKLtreatment. Parthenolide suppressed the expression of NFATc1,OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treatedBMMs. Furthermore, parthenolide down-regulated the stabilityof c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed theinhibitory effect of parthenolide on RANKL-mediated osteoclastdifferentiation. Parthenolide also inhibited the bone resorbingactivity of mature osteoclasts. Parthenolide inhibits thedifferentiation and bone-resolving activity of osteoclast byRANKL, suggesting its potential therapeutic value for bonedestructive disorders associated with osteoclast-mediated bone resorption.
Abstract
Parthenolide, a natural product derived from Feverfew, preventsseptic shock and inflammation. We aimed to identify the effectsof parthenolide on the RANKL (receptor activator of NF-κBligand)-induced differentiation and bone resorbing activity ofosteoclasts. In this study, parthenolide dose-dependentlyinhibited RANKL-mediated osteoclast differentiation in BMMs,without any evidence of cytotoxicity and the phosphorylation ofp38, ERK, and IκB, as well as IκB degradation by RANKLtreatment. Parthenolide suppressed the expression of NFATc1,OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treatedBMMs. Furthermore, parthenolide down-regulated the stabilityof c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed theinhibitory effect of parthenolide on RANKL-mediated osteoclastdifferentiation. Parthenolide also inhibited the bone resorbingactivity of mature osteoclasts. Parthenolide inhibits thedifferentiation and bone-resolving activity of osteoclast byRANKL, suggesting its potential therapeutic value for bonedestructive disorders associated with osteoclast-mediated bone resorption.
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