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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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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. |
format | Online Article Text |
id | pubmed-5797611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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