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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.
BMB Rep. 2014 Aug; 47(8):451-6.BR

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+Show Affiliations

Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine, Iksan 570-749, Korea.Department of Anatomy; BK21plus Program and Department of Smart Life-care Convergence Graduate School, Wonkwang University School of Medicine, Iksan 570-749, Korea.Imaging Science-based Lung and Bone Diseases Research Center; Department of Radiology, Wonkwang University School of Medicine, Iksan 570-749, Korea.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24314143

Citation

Kim, Ju-Young, et al. "Parthenolide Inhibits Osteoclast Differentiation and Bone Resorbing Activity By Down-regulation of NFATc1 Induction and c-Fos Stability, During RANKL-mediated Osteoclastogenesis." BMB Reports, vol. 47, no. 8, 2014, pp. 451-6.
Kim JY, Cheon YH, Yoon KH, et al. Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis. BMB Rep. 2014;47(8):451-6.
Kim, J. Y., Cheon, Y. H., Yoon, K. H., Lee, M. S., & Oh, J. (2014). Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis. BMB Reports, 47(8), 451-6.
Kim JY, et al. Parthenolide Inhibits Osteoclast Differentiation and Bone Resorbing Activity By Down-regulation of NFATc1 Induction and c-Fos Stability, During RANKL-mediated Osteoclastogenesis. BMB Rep. 2014;47(8):451-6. PubMed PMID: 24314143.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis. AU - Kim,Ju-Young, AU - Cheon,Yoon-Hee, AU - Yoon,Kwon-Ha, AU - Lee,Myeung Su, AU - Oh,Jaemin, PY - 2013/09/12/received PY - 2013/12/10/entrez PY - 2013/12/10/pubmed PY - 2015/5/13/medline SP - 451 EP - 6 JF - BMB reports JO - BMB Rep VL - 47 IS - 8 N2 - 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. SN - 1976-670X UR - https://www.unboundmedicine.com/medline/citation/24314143/Parthenolide_inhibits_osteoclast_differentiation_and_bone_resorbing_activity_by_down_regulation_of_NFATc1_induction_and_c_Fos_stability_during_RANKL_mediated_osteoclastogenesis_ L2 - http://www.bmbreports.org/journal/view.html?volume=47&number=8&spage=451 DB - PRIME DP - Unbound Medicine ER -