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Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo

Excessive bone resorption by osteoclasts contributes significantly to osteoclast-related diseases such as periprosthetic osteolysis and osteoporosis. Osteolysis in a titanium particle-induced calvarial model and bone loss in an ovariectomized mice model occurred similarly to those in humans; thus, t...

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Autores principales: Xu, Qiang, Chen, Guiping, Xu, Huaen, Xia, Guoming, Zhu, Meisong, Zhan, Haibo, Zhang, Bin, Dai, Min, Fan, Hongxian, Liu, Xuqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210420/
https://www.ncbi.nlm.nih.gov/pubmed/34149427
http://dx.doi.org/10.3389/fphar.2021.682541
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author Xu, Qiang
Chen, Guiping
Xu, Huaen
Xia, Guoming
Zhu, Meisong
Zhan, Haibo
Zhang, Bin
Dai, Min
Fan, Hongxian
Liu, Xuqiang
author_facet Xu, Qiang
Chen, Guiping
Xu, Huaen
Xia, Guoming
Zhu, Meisong
Zhan, Haibo
Zhang, Bin
Dai, Min
Fan, Hongxian
Liu, Xuqiang
author_sort Xu, Qiang
collection PubMed
description Excessive bone resorption by osteoclasts contributes significantly to osteoclast-related diseases such as periprosthetic osteolysis and osteoporosis. Osteolysis in a titanium particle-induced calvarial model and bone loss in an ovariectomized mice model occurred similarly to those in humans; thus, these models can be used to evaluate potential therapies for aseptic prosthetic loosening and osteoporosis. Celastrol, which is extracted from the seeds of the genus Tripterygium, has been thoroughly investigated for its anti-inflammatory and anti-cancer pharmacological effects. However, the mechanisms involving bone metabolism by which celastrol inhibits osteoclastogenesis are not yet fully understood. We demonstrated that celastrol inhibited the receptor activator of nuclear factor κB ligand-induced osteoclastogenesis and the bone resorptive function of osteoclasts in vitro by inhibiting the activation of transforming growth factor β-activated kinase 1-mediated NF-κB and mitogen-activated protein kinase signaling pathways and downregulating osteoclastogenesis marker-related genes. Furthermore, celastrol was also shown to be beneficial in both the titanium particle-induced osteolysis calvarial and the murine ovariectomy-induced bone loss. Collectively, our results suggested that celastrol is promising for the prevention of aseptic prosthetic loosening and osteoporosis in the treatment of osteolytic diseases induced by disrupted osteoclast formation and function.
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spelling pubmed-82104202021-06-18 Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo Xu, Qiang Chen, Guiping Xu, Huaen Xia, Guoming Zhu, Meisong Zhan, Haibo Zhang, Bin Dai, Min Fan, Hongxian Liu, Xuqiang Front Pharmacol Pharmacology Excessive bone resorption by osteoclasts contributes significantly to osteoclast-related diseases such as periprosthetic osteolysis and osteoporosis. Osteolysis in a titanium particle-induced calvarial model and bone loss in an ovariectomized mice model occurred similarly to those in humans; thus, these models can be used to evaluate potential therapies for aseptic prosthetic loosening and osteoporosis. Celastrol, which is extracted from the seeds of the genus Tripterygium, has been thoroughly investigated for its anti-inflammatory and anti-cancer pharmacological effects. However, the mechanisms involving bone metabolism by which celastrol inhibits osteoclastogenesis are not yet fully understood. We demonstrated that celastrol inhibited the receptor activator of nuclear factor κB ligand-induced osteoclastogenesis and the bone resorptive function of osteoclasts in vitro by inhibiting the activation of transforming growth factor β-activated kinase 1-mediated NF-κB and mitogen-activated protein kinase signaling pathways and downregulating osteoclastogenesis marker-related genes. Furthermore, celastrol was also shown to be beneficial in both the titanium particle-induced osteolysis calvarial and the murine ovariectomy-induced bone loss. Collectively, our results suggested that celastrol is promising for the prevention of aseptic prosthetic loosening and osteoporosis in the treatment of osteolytic diseases induced by disrupted osteoclast formation and function. Frontiers Media S.A. 2021-06-03 /pmc/articles/PMC8210420/ /pubmed/34149427 http://dx.doi.org/10.3389/fphar.2021.682541 Text en Copyright © 2021 Xu, Chen, Xu, Xia, Zhu, Zhan, Zhang, Dai, Fan and Liu. https://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) and the copyright owner(s) 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
Xu, Qiang
Chen, Guiping
Xu, Huaen
Xia, Guoming
Zhu, Meisong
Zhan, Haibo
Zhang, Bin
Dai, Min
Fan, Hongxian
Liu, Xuqiang
Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo
title Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo
title_full Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo
title_fullStr Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo
title_full_unstemmed Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo
title_short Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo
title_sort celastrol attenuates rankl-induced osteoclastogenesis in vitro and reduces titanium particle-induced osteolysis and ovariectomy-induced bone loss in vivo
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210420/
https://www.ncbi.nlm.nih.gov/pubmed/34149427
http://dx.doi.org/10.3389/fphar.2021.682541
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