title: Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis.
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-κB 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 IκB, as well as IκB 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.
authors: Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine, Iksan 570-749, Korea.
authors: Ju-Young
authors: JY
authors: Kim
authors: Department of Anatomy; BK21plus Program and Department of Smart Life-care Convergence Graduate School, Wonkwang University School of Medicine, Iksan 570-749, Korea.
authors: Yoon-Hee
authors: YH
authors: Cheon
authors: Imaging Science-based Lung and Bone Diseases Research Center; Department of Radiology, Wonkwang University School of Medicine, Iksan 570-749, Korea.
authors: Kwon-Ha
authors: KH
authors: Yoon
authors: Imaging Science-based Lung and Bone Diseases Research Center; Institute for Skeletal Disease; Department of Rheumatology, Wonkwang University School of Medicine, Iksan 570-749, Korea.
authors: Myeung Su
authors: MS
authors: Lee
authors: Imaging Science-based Lung and Bone Diseases Research Center; Department of Anatomy; BK21plus Program and Department of Smart Life-care Convergence Graduate School; Institute for Skeletal Disease, Wonkwang University School of Medicine, Iksan 570-749, Korea.
authors: Jaemin
authors: J
authors: Oh
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D012717:Sesquiterpenes; C002669:parthenolide; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D056657:Cathepsin K