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Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption

Periodontitis is a chronic inflammatory disease that damages the integrity of the tooth-supporting tissues, known as the periodontium, and comprising the gingiva, periodontal ligament and alveolar bone. In this study, the effects of nardosinone (Nd) on bone were tested in a model of lipopolysacchari...

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Autores principales: Niu, Chenguang, Xiao, Fei, Yuan, Keyong, Hu, XuChen, Lin, Wenzhen, Ma, Rui, Zhang, Xiaoling, Huang, Zhengwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601052/
https://www.ncbi.nlm.nih.gov/pubmed/28955231
http://dx.doi.org/10.3389/fphar.2017.00626
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author Niu, Chenguang
Xiao, Fei
Yuan, Keyong
Hu, XuChen
Lin, Wenzhen
Ma, Rui
Zhang, Xiaoling
Huang, Zhengwei
author_facet Niu, Chenguang
Xiao, Fei
Yuan, Keyong
Hu, XuChen
Lin, Wenzhen
Ma, Rui
Zhang, Xiaoling
Huang, Zhengwei
author_sort Niu, Chenguang
collection PubMed
description Periodontitis is a chronic inflammatory disease that damages the integrity of the tooth-supporting tissues, known as the periodontium, and comprising the gingiva, periodontal ligament and alveolar bone. In this study, the effects of nardosinone (Nd) on bone were tested in a model of lipopolysaccharide (LPS)-induced alveolar bone loss, and the associated mechanisms were elucidated. Nd effectively suppressed LPS-induced alveolar bone loss and reduced osteoclast (OC) numbers in vivo. Nd suppressed receptor activator of nuclear factor-κB ligand (RANKL)-mediated OC differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner. Further investigation revealed that Nd suppressed osteoclastogenesis by suppressing the ERK and JNK signaling pathways, scavenging reactive oxygen species, and suppressing the activation of PLCγ2 that consequently affects the expression and/or activity of the OC-specific transcription factors, c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). In addition, Nd significantly reduced the expression of OC-specific markers in mouse bone marrow-derived pre-OCs, including c-Fos, cathepsin K (Ctsk), VATPase d2, and Nfatc1. Collectively, these findings suggest that Nd has beneficial effects on bone, and the suppression of OC number implies that the effect is exerted directly on osteoclastogenesis.
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spelling pubmed-56010522017-09-27 Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption Niu, Chenguang Xiao, Fei Yuan, Keyong Hu, XuChen Lin, Wenzhen Ma, Rui Zhang, Xiaoling Huang, Zhengwei Front Pharmacol Pharmacology Periodontitis is a chronic inflammatory disease that damages the integrity of the tooth-supporting tissues, known as the periodontium, and comprising the gingiva, periodontal ligament and alveolar bone. In this study, the effects of nardosinone (Nd) on bone were tested in a model of lipopolysaccharide (LPS)-induced alveolar bone loss, and the associated mechanisms were elucidated. Nd effectively suppressed LPS-induced alveolar bone loss and reduced osteoclast (OC) numbers in vivo. Nd suppressed receptor activator of nuclear factor-κB ligand (RANKL)-mediated OC differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner. Further investigation revealed that Nd suppressed osteoclastogenesis by suppressing the ERK and JNK signaling pathways, scavenging reactive oxygen species, and suppressing the activation of PLCγ2 that consequently affects the expression and/or activity of the OC-specific transcription factors, c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). In addition, Nd significantly reduced the expression of OC-specific markers in mouse bone marrow-derived pre-OCs, including c-Fos, cathepsin K (Ctsk), VATPase d2, and Nfatc1. Collectively, these findings suggest that Nd has beneficial effects on bone, and the suppression of OC number implies that the effect is exerted directly on osteoclastogenesis. Frontiers Media S.A. 2017-09-12 /pmc/articles/PMC5601052/ /pubmed/28955231 http://dx.doi.org/10.3389/fphar.2017.00626 Text en Copyright © 2017 Niu, Xiao, Yuan, Hu, Lin, Ma, Zhang and Huang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Niu, Chenguang
Xiao, Fei
Yuan, Keyong
Hu, XuChen
Lin, Wenzhen
Ma, Rui
Zhang, Xiaoling
Huang, Zhengwei
Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption
title Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption
title_full Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption
title_fullStr Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption
title_full_unstemmed Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption
title_short Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption
title_sort nardosinone suppresses rankl-induced osteoclastogenesis and attenuates lipopolysaccharide-induced alveolar bone resorption
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601052/
https://www.ncbi.nlm.nih.gov/pubmed/28955231
http://dx.doi.org/10.3389/fphar.2017.00626
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