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A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5

Post-menopausal osteoporosis (PMOP) is a metabolic bone disorder characterized by low bone mass and micro-architectural deterioration of bone tissue. The over-activated osteoclastogenesis, which plays an important role in osteoporosis, has become an important therapeutic target. M54 was a bioactive...

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Autores principales: Xin, Zhi, Jin, Cui, Chao, Liu, Zheng, Zhang, Liehu, Cao, Panpan, Pan, Weizong, Weng, Xiao, Zhai, Qingjie, Zhao, Honggang, Hu, Longjuan, Qin, Xiao, Chen, Jiacan, Su
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797611/
https://www.ncbi.nlm.nih.gov/pubmed/29441015
http://dx.doi.org/10.3389/fphar.2018.00022
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author Xin, Zhi
Jin, Cui
Chao, Liu
Zheng, Zhang
Liehu, Cao
Panpan, Pan
Weizong, Weng
Xiao, Zhai
Qingjie, Zhao
Honggang, Hu
Longjuan, Qin
Xiao, Chen
Jiacan, Su
author_facet Xin, Zhi
Jin, Cui
Chao, Liu
Zheng, Zhang
Liehu, Cao
Panpan, Pan
Weizong, Weng
Xiao, Zhai
Qingjie, Zhao
Honggang, Hu
Longjuan, Qin
Xiao, Chen
Jiacan, Su
author_sort Xin, Zhi
collection PubMed
description Post-menopausal osteoporosis (PMOP) is a metabolic bone disorder characterized by low bone mass and micro-architectural deterioration of bone tissue. The over-activated osteoclastogenesis, which plays an important role in osteoporosis, has become an important therapeutic target. M54 was a bioactive derivative of the Chinese traditional herb matrine. We found that M54 could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells and RAW264.7 cells through suppressing NF-κB, PI3K/AKT, and MAPKs pathways activity in vitro, and prevent ovariectomy-induced bone loss in vivo. Our previous study has proved that ribosomal protein S5 (RPS5) was a direct target of M19, based on which M54 was synthesized. Thus we deduced that M54 also targeted RPS5. During osteoclastogenesis, the RPS5 level in RAW264.7 cells was significantly down-regulated while M54 could maintain its level. After RPS5 was silenced, the inhibitory effects of M54 on osteoclastogenesis were partially compromised, indicating that M54 took effects through targeting RPS5. In summary, M54 was a potential clinical medicine for post-menopause osteoporosis treatment, and RPS5 is a possible key protein in PMOP.
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spelling pubmed-57976112018-02-13 A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5 Xin, Zhi Jin, Cui Chao, Liu Zheng, Zhang Liehu, Cao Panpan, Pan Weizong, Weng Xiao, Zhai Qingjie, Zhao Honggang, Hu Longjuan, Qin Xiao, Chen Jiacan, Su Front Pharmacol Pharmacology Post-menopausal osteoporosis (PMOP) is a metabolic bone disorder characterized by low bone mass and micro-architectural deterioration of bone tissue. The over-activated osteoclastogenesis, which plays an important role in osteoporosis, has become an important therapeutic target. M54 was a bioactive derivative of the Chinese traditional herb matrine. We found that M54 could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells and RAW264.7 cells through suppressing NF-κB, PI3K/AKT, and MAPKs pathways activity in vitro, and prevent ovariectomy-induced bone loss in vivo. Our previous study has proved that ribosomal protein S5 (RPS5) was a direct target of M19, based on which M54 was synthesized. Thus we deduced that M54 also targeted RPS5. During osteoclastogenesis, the RPS5 level in RAW264.7 cells was significantly down-regulated while M54 could maintain its level. After RPS5 was silenced, the inhibitory effects of M54 on osteoclastogenesis were partially compromised, indicating that M54 took effects through targeting RPS5. In summary, M54 was a potential clinical medicine for post-menopause osteoporosis treatment, and RPS5 is a possible key protein in PMOP. Frontiers Media S.A. 2018-01-30 /pmc/articles/PMC5797611/ /pubmed/29441015 http://dx.doi.org/10.3389/fphar.2018.00022 Text en Copyright © 2018 Xin, Jin, Chao, Zheng, Liehu, Panpan, Weizong, Xiao, Qingjie, Honggang, Longjuan, Xiao and Jiacan. 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 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
Xin, Zhi
Jin, Cui
Chao, Liu
Zheng, Zhang
Liehu, Cao
Panpan, Pan
Weizong, Weng
Xiao, Zhai
Qingjie, Zhao
Honggang, Hu
Longjuan, Qin
Xiao, Chen
Jiacan, Su
A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5
title A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5
title_full A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5
title_fullStr A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5
title_full_unstemmed A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5
title_short A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5
title_sort matrine derivative m54 suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by targeting ribosomal protein s5
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797611/
https://www.ncbi.nlm.nih.gov/pubmed/29441015
http://dx.doi.org/10.3389/fphar.2018.00022
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