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Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis
Metformin, a cost-effective and safe orally administered antidiabetic drug used by millions of patients, has exhibited great interest for its potential osteogenic-promoting properties in different types of cells, including mesenchymal stem cells (MSCs). Diabetic osteopathy is a common comorbidity of...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453594/ https://www.ncbi.nlm.nih.gov/pubmed/32945402 http://dx.doi.org/10.3892/mmr.2020.11391 |
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author | Zhou, Renyi Ma, Yue Qiu, Shui Gong, Zunlei Zhou, Xiaoshu |
author_facet | Zhou, Renyi Ma, Yue Qiu, Shui Gong, Zunlei Zhou, Xiaoshu |
author_sort | Zhou, Renyi |
collection | PubMed |
description | Metformin, a cost-effective and safe orally administered antidiabetic drug used by millions of patients, has exhibited great interest for its potential osteogenic-promoting properties in different types of cells, including mesenchymal stem cells (MSCs). Diabetic osteopathy is a common comorbidity of diabetes mellitus; however, the underlying molecular mechanisms of metformin on the physiological processes of MSCs, under high glucose condition, remain unknown. To determine the effects of metformin on the regulatory roles of proliferation and differentiation in MSCs, under high glucose conditions, osteogenesis after metformin treatment was detected with Alizarin Red S and ALP staining. The results demonstrated that high glucose levels significantly inhibited cell proliferation and osteogenic differentiation under high glucose conditions. Notably, addition of metformin reversed the inhibitory effects induced by high glucose levels on cell proliferation and osteogenesis. Furthermore, high glucose levels significantly decreased mitochondrial membrane potential (MMP), whereas treatment with metformin helped maintain MMP. Further analysis of mitochondrial function revealed that metformin significantly promoted ATP synthesis, mitochondrial DNA mass and mitochondrial transcriptional activity, which were inhibited by high glucose culture. Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis. Taken together, the results of the present study demonstrated the protective role of metformin on the physiological processes of MSCs, under high glucose condition and highlighted the potential molecular mechanism underlying the effect of metformin in promoting cell proliferation and osteogenesis under high glucose condition. |
format | Online Article Text |
id | pubmed-7453594 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-74535942020-08-31 Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis Zhou, Renyi Ma, Yue Qiu, Shui Gong, Zunlei Zhou, Xiaoshu Mol Med Rep Articles Metformin, a cost-effective and safe orally administered antidiabetic drug used by millions of patients, has exhibited great interest for its potential osteogenic-promoting properties in different types of cells, including mesenchymal stem cells (MSCs). Diabetic osteopathy is a common comorbidity of diabetes mellitus; however, the underlying molecular mechanisms of metformin on the physiological processes of MSCs, under high glucose condition, remain unknown. To determine the effects of metformin on the regulatory roles of proliferation and differentiation in MSCs, under high glucose conditions, osteogenesis after metformin treatment was detected with Alizarin Red S and ALP staining. The results demonstrated that high glucose levels significantly inhibited cell proliferation and osteogenic differentiation under high glucose conditions. Notably, addition of metformin reversed the inhibitory effects induced by high glucose levels on cell proliferation and osteogenesis. Furthermore, high glucose levels significantly decreased mitochondrial membrane potential (MMP), whereas treatment with metformin helped maintain MMP. Further analysis of mitochondrial function revealed that metformin significantly promoted ATP synthesis, mitochondrial DNA mass and mitochondrial transcriptional activity, which were inhibited by high glucose culture. Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis. Taken together, the results of the present study demonstrated the protective role of metformin on the physiological processes of MSCs, under high glucose condition and highlighted the potential molecular mechanism underlying the effect of metformin in promoting cell proliferation and osteogenesis under high glucose condition. D.A. Spandidos 2020-10 2020-07-30 /pmc/articles/PMC7453594/ /pubmed/32945402 http://dx.doi.org/10.3892/mmr.2020.11391 Text en Copyright: © Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Zhou, Renyi Ma, Yue Qiu, Shui Gong, Zunlei Zhou, Xiaoshu Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis |
title | Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis |
title_full | Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis |
title_fullStr | Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis |
title_full_unstemmed | Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis |
title_short | Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis |
title_sort | metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ros-akt-mtor axis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453594/ https://www.ncbi.nlm.nih.gov/pubmed/32945402 http://dx.doi.org/10.3892/mmr.2020.11391 |
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