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Madecassoside inhibits estrogen deficiency‐induced osteoporosis by suppressing RANKL‐induced osteoclastogenesis
Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Madecassoside (MA), isolated from Centella asiatica, was reported to have anti‐inflammatory and antioxidant activities, bu...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307845/ https://www.ncbi.nlm.nih.gov/pubmed/30338925 http://dx.doi.org/10.1111/jcmm.13942 |
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author | Wang, Qingqing Yao, Lingya Xu, Ke Jin, Haiming Chen, Kai Wang, Ziyi Liu, Qian Cao, Zhen kenny, Jacob Liu, Yuhao Tickner, Jennifer Xu, Huazi Xu, Jiake |
author_facet | Wang, Qingqing Yao, Lingya Xu, Ke Jin, Haiming Chen, Kai Wang, Ziyi Liu, Qian Cao, Zhen kenny, Jacob Liu, Yuhao Tickner, Jennifer Xu, Huazi Xu, Jiake |
author_sort | Wang, Qingqing |
collection | PubMed |
description | Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Madecassoside (MA), isolated from Centella asiatica, was reported to have anti‐inflammatory and antioxidant activities, but its role in osteoporosis treatment has not yet been confirmed. In our study, MA was found to have an inhibitory effect on the RANKL‐induced formation and function of OCs in a dose‐dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c‐Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption‐related genes and proteins (Acp5/TRAcP, CTSK, ATP6V0D2/V‐ATPase‐d2, and integrin β3). Furthermore, we examined the underlying mechanisms and found that MA represses osteoclastogenesis by blocking Ca(2+) oscillations and the NF‐κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL‐mediated osteoclastogenesis and the underlying mechanisms, MA might be a potential candidate for treating osteolytic bone diseases. |
format | Online Article Text |
id | pubmed-6307845 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63078452019-01-04 Madecassoside inhibits estrogen deficiency‐induced osteoporosis by suppressing RANKL‐induced osteoclastogenesis Wang, Qingqing Yao, Lingya Xu, Ke Jin, Haiming Chen, Kai Wang, Ziyi Liu, Qian Cao, Zhen kenny, Jacob Liu, Yuhao Tickner, Jennifer Xu, Huazi Xu, Jiake J Cell Mol Med Original Articles Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Madecassoside (MA), isolated from Centella asiatica, was reported to have anti‐inflammatory and antioxidant activities, but its role in osteoporosis treatment has not yet been confirmed. In our study, MA was found to have an inhibitory effect on the RANKL‐induced formation and function of OCs in a dose‐dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c‐Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption‐related genes and proteins (Acp5/TRAcP, CTSK, ATP6V0D2/V‐ATPase‐d2, and integrin β3). Furthermore, we examined the underlying mechanisms and found that MA represses osteoclastogenesis by blocking Ca(2+) oscillations and the NF‐κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL‐mediated osteoclastogenesis and the underlying mechanisms, MA might be a potential candidate for treating osteolytic bone diseases. John Wiley and Sons Inc. 2018-10-19 2019-01 /pmc/articles/PMC6307845/ /pubmed/30338925 http://dx.doi.org/10.1111/jcmm.13942 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Wang, Qingqing Yao, Lingya Xu, Ke Jin, Haiming Chen, Kai Wang, Ziyi Liu, Qian Cao, Zhen kenny, Jacob Liu, Yuhao Tickner, Jennifer Xu, Huazi Xu, Jiake Madecassoside inhibits estrogen deficiency‐induced osteoporosis by suppressing RANKL‐induced osteoclastogenesis |
title | Madecassoside inhibits estrogen deficiency‐induced osteoporosis by suppressing RANKL‐induced osteoclastogenesis |
title_full | Madecassoside inhibits estrogen deficiency‐induced osteoporosis by suppressing RANKL‐induced osteoclastogenesis |
title_fullStr | Madecassoside inhibits estrogen deficiency‐induced osteoporosis by suppressing RANKL‐induced osteoclastogenesis |
title_full_unstemmed | Madecassoside inhibits estrogen deficiency‐induced osteoporosis by suppressing RANKL‐induced osteoclastogenesis |
title_short | Madecassoside inhibits estrogen deficiency‐induced osteoporosis by suppressing RANKL‐induced osteoclastogenesis |
title_sort | madecassoside inhibits estrogen deficiency‐induced osteoporosis by suppressing rankl‐induced osteoclastogenesis |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307845/ https://www.ncbi.nlm.nih.gov/pubmed/30338925 http://dx.doi.org/10.1111/jcmm.13942 |
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