Cargando…

Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice

Aconitum pseudo-laeve var. erectum (APE) has been widely shown in herbal medicine to have a therapeutic effect on inflammatory conditions. However, there has been no evidence on whether the extract of APE is involved in the biological bone metabolism process, particularly osteoclast-mediated bone re...

Descripción completa

Detalles Bibliográficos
Autores principales: Baek, Jong Min, Kim, Ju-Young, Cheon, Yoon-Hee, Park, Sun-Hyang, Ahn, Sung-Jun, Yoon, Kwon-Ha, Oh, Jaemin, Lee, Myeung Su
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270969/
https://www.ncbi.nlm.nih.gov/pubmed/25100255
http://dx.doi.org/10.3390/molecules190811628
_version_ 1783376820658241536
author Baek, Jong Min
Kim, Ju-Young
Cheon, Yoon-Hee
Park, Sun-Hyang
Ahn, Sung-Jun
Yoon, Kwon-Ha
Oh, Jaemin
Lee, Myeung Su
author_facet Baek, Jong Min
Kim, Ju-Young
Cheon, Yoon-Hee
Park, Sun-Hyang
Ahn, Sung-Jun
Yoon, Kwon-Ha
Oh, Jaemin
Lee, Myeung Su
author_sort Baek, Jong Min
collection PubMed
description Aconitum pseudo-laeve var. erectum (APE) has been widely shown in herbal medicine to have a therapeutic effect on inflammatory conditions. However, there has been no evidence on whether the extract of APE is involved in the biological bone metabolism process, particularly osteoclast-mediated bone resorption. In this study, we confirmed that the administration of APE could restore normal skeletal conditions in a murine model of lipopolysaccharide (LPS)-induced bone loss via a decrease in the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio and osteoclast number. We then investigated the effect of APE on the RANKL-induced formation and function of osteoclasts to elucidate its underlying molecular mechanisms. APE suppressed the formation of tartrate-resistant acid phosphatase (TRAP)-positive cells, as well as the bone-resorbing activity of mature osteoclasts. Furthermore, APE attenuated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and c-Fos without affecting any early signal pathway of osteoclastogenesis. Subsequently, APE significantly downregulated the expression of various genes exclusively expressed in osteoclasts. These results demonstrate that APE restores LPS-induced bone loss through a decrease of the serum RANKL/OPG ratio, and inhibits osteoclast differentiation and function, suggesting the promise of APE as a potential cure for various osteoclast-associated bone diseases.
format Online
Article
Text
id pubmed-6270969
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62709692018-12-27 Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice Baek, Jong Min Kim, Ju-Young Cheon, Yoon-Hee Park, Sun-Hyang Ahn, Sung-Jun Yoon, Kwon-Ha Oh, Jaemin Lee, Myeung Su Molecules Article Aconitum pseudo-laeve var. erectum (APE) has been widely shown in herbal medicine to have a therapeutic effect on inflammatory conditions. However, there has been no evidence on whether the extract of APE is involved in the biological bone metabolism process, particularly osteoclast-mediated bone resorption. In this study, we confirmed that the administration of APE could restore normal skeletal conditions in a murine model of lipopolysaccharide (LPS)-induced bone loss via a decrease in the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio and osteoclast number. We then investigated the effect of APE on the RANKL-induced formation and function of osteoclasts to elucidate its underlying molecular mechanisms. APE suppressed the formation of tartrate-resistant acid phosphatase (TRAP)-positive cells, as well as the bone-resorbing activity of mature osteoclasts. Furthermore, APE attenuated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and c-Fos without affecting any early signal pathway of osteoclastogenesis. Subsequently, APE significantly downregulated the expression of various genes exclusively expressed in osteoclasts. These results demonstrate that APE restores LPS-induced bone loss through a decrease of the serum RANKL/OPG ratio, and inhibits osteoclast differentiation and function, suggesting the promise of APE as a potential cure for various osteoclast-associated bone diseases. MDPI 2014-08-05 /pmc/articles/PMC6270969/ /pubmed/25100255 http://dx.doi.org/10.3390/molecules190811628 Text en © 2014 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Baek, Jong Min
Kim, Ju-Young
Cheon, Yoon-Hee
Park, Sun-Hyang
Ahn, Sung-Jun
Yoon, Kwon-Ha
Oh, Jaemin
Lee, Myeung Su
Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice
title Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice
title_full Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice
title_fullStr Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice
title_full_unstemmed Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice
title_short Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice
title_sort aconitum pseudo-laeve var. erectum inhibits receptor activator of nuclear factor kappa-b ligand-induced osteoclastogenesis via the c-fos/nuclear factor of activated t-cells, cytoplasmic 1 signaling pathway and prevents lipopolysaccharide-induced bone loss in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270969/
https://www.ncbi.nlm.nih.gov/pubmed/25100255
http://dx.doi.org/10.3390/molecules190811628
work_keys_str_mv AT baekjongmin aconitumpseudolaevevarerectuminhibitsreceptoractivatorofnuclearfactorkappabligandinducedosteoclastogenesisviathecfosnuclearfactorofactivatedtcellscytoplasmic1signalingpathwayandpreventslipopolysaccharideinducedbonelossinmice
AT kimjuyoung aconitumpseudolaevevarerectuminhibitsreceptoractivatorofnuclearfactorkappabligandinducedosteoclastogenesisviathecfosnuclearfactorofactivatedtcellscytoplasmic1signalingpathwayandpreventslipopolysaccharideinducedbonelossinmice
AT cheonyoonhee aconitumpseudolaevevarerectuminhibitsreceptoractivatorofnuclearfactorkappabligandinducedosteoclastogenesisviathecfosnuclearfactorofactivatedtcellscytoplasmic1signalingpathwayandpreventslipopolysaccharideinducedbonelossinmice
AT parksunhyang aconitumpseudolaevevarerectuminhibitsreceptoractivatorofnuclearfactorkappabligandinducedosteoclastogenesisviathecfosnuclearfactorofactivatedtcellscytoplasmic1signalingpathwayandpreventslipopolysaccharideinducedbonelossinmice
AT ahnsungjun aconitumpseudolaevevarerectuminhibitsreceptoractivatorofnuclearfactorkappabligandinducedosteoclastogenesisviathecfosnuclearfactorofactivatedtcellscytoplasmic1signalingpathwayandpreventslipopolysaccharideinducedbonelossinmice
AT yoonkwonha aconitumpseudolaevevarerectuminhibitsreceptoractivatorofnuclearfactorkappabligandinducedosteoclastogenesisviathecfosnuclearfactorofactivatedtcellscytoplasmic1signalingpathwayandpreventslipopolysaccharideinducedbonelossinmice
AT ohjaemin aconitumpseudolaevevarerectuminhibitsreceptoractivatorofnuclearfactorkappabligandinducedosteoclastogenesisviathecfosnuclearfactorofactivatedtcellscytoplasmic1signalingpathwayandpreventslipopolysaccharideinducedbonelossinmice
AT leemyeungsu aconitumpseudolaevevarerectuminhibitsreceptoractivatorofnuclearfactorkappabligandinducedosteoclastogenesisviathecfosnuclearfactorofactivatedtcellscytoplasmic1signalingpathwayandpreventslipopolysaccharideinducedbonelossinmice