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Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis

Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activ...

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Autores principales: Zhong, Zeyuan, Qian, Zhi, Zhang, Xu, Chen, Fancheng, Ni, Shuo, Kang, Zhanrong, Zhang, Fangxue, Li, Dejian, Yu, Baoqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6967024/
https://www.ncbi.nlm.nih.gov/pubmed/31998129
http://dx.doi.org/10.3389/fphar.2019.01530
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author Zhong, Zeyuan
Qian, Zhi
Zhang, Xu
Chen, Fancheng
Ni, Shuo
Kang, Zhanrong
Zhang, Fangxue
Li, Dejian
Yu, Baoqing
author_facet Zhong, Zeyuan
Qian, Zhi
Zhang, Xu
Chen, Fancheng
Ni, Shuo
Kang, Zhanrong
Zhang, Fangxue
Li, Dejian
Yu, Baoqing
author_sort Zhong, Zeyuan
collection PubMed
description Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activator of NF-kB ligand (RANKL)/Osteoprotegerin (OPG), which then leads to the overactivation of osteoclastogenesis. Tetrandrine, a bis-benzylisoquinoline alkaloid, has been widely used in the treatment of rheumatoid arthritis clinically in China. Here, we demonstrate that tetrandrine significantly prevented ovariectomy-induced bone loss and inhibited RANKL-induced osteoclastogenesis. In vivo, we found that intraperitoneal injection of tetrandrine (30 mg/kg) every other day markedly reduced bone loss in ovariectomized mice and the serum levels of TRAcp5b, TNF-a, IL-6, CTX-I, and RANKL/OPG were significantly decreased. In vitro, we found that tetrandrine significantly inhibited osteoclast differentiation in bone marrow monocytes (BMMs) and RAW264.7 cells according to the results of osteoclastogenesis‐related gene expression, tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption assay. Mechanistically, tetrandrine inhibited RANKL‐induced osteoclastogenesis by suppressing NF-kB, Ca2(+), PI3K/AKT, and MAPKs signaling pathways. Taken together, our findings suggest that tetrandrine suppresses osteoclastogenesis through modulation of multiple pathways and has potential value as a therapeutic agent for PMOP, especially for those suffering from RA and PMOP at the same time.
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spelling pubmed-69670242020-01-29 Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis Zhong, Zeyuan Qian, Zhi Zhang, Xu Chen, Fancheng Ni, Shuo Kang, Zhanrong Zhang, Fangxue Li, Dejian Yu, Baoqing Front Pharmacol Pharmacology Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activator of NF-kB ligand (RANKL)/Osteoprotegerin (OPG), which then leads to the overactivation of osteoclastogenesis. Tetrandrine, a bis-benzylisoquinoline alkaloid, has been widely used in the treatment of rheumatoid arthritis clinically in China. Here, we demonstrate that tetrandrine significantly prevented ovariectomy-induced bone loss and inhibited RANKL-induced osteoclastogenesis. In vivo, we found that intraperitoneal injection of tetrandrine (30 mg/kg) every other day markedly reduced bone loss in ovariectomized mice and the serum levels of TRAcp5b, TNF-a, IL-6, CTX-I, and RANKL/OPG were significantly decreased. In vitro, we found that tetrandrine significantly inhibited osteoclast differentiation in bone marrow monocytes (BMMs) and RAW264.7 cells according to the results of osteoclastogenesis‐related gene expression, tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption assay. Mechanistically, tetrandrine inhibited RANKL‐induced osteoclastogenesis by suppressing NF-kB, Ca2(+), PI3K/AKT, and MAPKs signaling pathways. Taken together, our findings suggest that tetrandrine suppresses osteoclastogenesis through modulation of multiple pathways and has potential value as a therapeutic agent for PMOP, especially for those suffering from RA and PMOP at the same time. Frontiers Media S.A. 2020-01-10 /pmc/articles/PMC6967024/ /pubmed/31998129 http://dx.doi.org/10.3389/fphar.2019.01530 Text en Copyright © 2020 Zhong, Qian, Zhang, Chen, Ni, Kang, Zhang, Li and Yu 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) 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
Zhong, Zeyuan
Qian, Zhi
Zhang, Xu
Chen, Fancheng
Ni, Shuo
Kang, Zhanrong
Zhang, Fangxue
Li, Dejian
Yu, Baoqing
Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis
title Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis
title_full Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis
title_fullStr Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis
title_full_unstemmed Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis
title_short Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis
title_sort tetrandrine prevents bone loss in ovariectomized mice by inhibiting rankl-induced osteoclastogenesis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6967024/
https://www.ncbi.nlm.nih.gov/pubmed/31998129
http://dx.doi.org/10.3389/fphar.2019.01530
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