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Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions

With rapidly ageing populations worldwide, the incidence of osteoporosis has reached epidemic proportions. Reactive oxygen species (ROS), a by‐product of oxidative stress and ageing, has been thought to induce osteoporosis by inhibiting osteogenic differentiation of mesenchymal stem cells (MSCs). Ho...

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Autores principales: Lin, Chia‐Hua, Li, Nan‐Ting, Cheng, Hui‐Shan, Yen, Men‐Luh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783884/
https://www.ncbi.nlm.nih.gov/pubmed/28975701
http://dx.doi.org/10.1111/jcmm.13356
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author Lin, Chia‐Hua
Li, Nan‐Ting
Cheng, Hui‐Shan
Yen, Men‐Luh
author_facet Lin, Chia‐Hua
Li, Nan‐Ting
Cheng, Hui‐Shan
Yen, Men‐Luh
author_sort Lin, Chia‐Hua
collection PubMed
description With rapidly ageing populations worldwide, the incidence of osteoporosis has reached epidemic proportions. Reactive oxygen species (ROS), a by‐product of oxidative stress and ageing, has been thought to induce osteoporosis by inhibiting osteogenic differentiation of mesenchymal stem cells (MSCs). However, specific mechanisms of how ROS results in alterations on MSC differentiation capacity have been inconsistently reported. We found that H(2)O(2), an ROS, simultaneously induced MSC lineage commitment towards adipogenesis and away from osteogenesis at the functional as well as transcriptional level. In addition, H(2)O(2) decreased the activities of SIRT1, a histone deacetylase and longevity gene. By silencing and reconstituting SIRT1 in MSCs, we demonstrated that H(2)O(2) exerted its disparate effects on adipogenic/osteoblastic lineage commitment mainly through modulating SIRT1 expression levels. Treatment with resveratrol, a SIRT1 agonist, can also reverse this ROS‐induced adipogenesis/osteogenesis lineage imbalance. Moreover, SIRT1 regulation of RUNX2 transcriptional activity was mediated through deacetylation of the ROS‐sensitive transcription factor FOXO3a. Taken together, our data implicate SIRT1 as playing a vital role in ROS‐directed lineage commitment of MSCs by modulating two lineages simultaneously. Our findings on the critical role of SIRT1 in ROS/age‐related perturbations of MSC differentiation capacity highlight this molecule as a target for maintenance of MSC stemness as well as a potential anabolic target in osteoporosis.
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spelling pubmed-57838842018-02-08 Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions Lin, Chia‐Hua Li, Nan‐Ting Cheng, Hui‐Shan Yen, Men‐Luh J Cell Mol Med Original Articles With rapidly ageing populations worldwide, the incidence of osteoporosis has reached epidemic proportions. Reactive oxygen species (ROS), a by‐product of oxidative stress and ageing, has been thought to induce osteoporosis by inhibiting osteogenic differentiation of mesenchymal stem cells (MSCs). However, specific mechanisms of how ROS results in alterations on MSC differentiation capacity have been inconsistently reported. We found that H(2)O(2), an ROS, simultaneously induced MSC lineage commitment towards adipogenesis and away from osteogenesis at the functional as well as transcriptional level. In addition, H(2)O(2) decreased the activities of SIRT1, a histone deacetylase and longevity gene. By silencing and reconstituting SIRT1 in MSCs, we demonstrated that H(2)O(2) exerted its disparate effects on adipogenic/osteoblastic lineage commitment mainly through modulating SIRT1 expression levels. Treatment with resveratrol, a SIRT1 agonist, can also reverse this ROS‐induced adipogenesis/osteogenesis lineage imbalance. Moreover, SIRT1 regulation of RUNX2 transcriptional activity was mediated through deacetylation of the ROS‐sensitive transcription factor FOXO3a. Taken together, our data implicate SIRT1 as playing a vital role in ROS‐directed lineage commitment of MSCs by modulating two lineages simultaneously. Our findings on the critical role of SIRT1 in ROS/age‐related perturbations of MSC differentiation capacity highlight this molecule as a target for maintenance of MSC stemness as well as a potential anabolic target in osteoporosis. John Wiley and Sons Inc. 2017-10-03 2018-02 /pmc/articles/PMC5783884/ /pubmed/28975701 http://dx.doi.org/10.1111/jcmm.13356 Text en © 2017 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 Creative Commons Attribution (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
Lin, Chia‐Hua
Li, Nan‐Ting
Cheng, Hui‐Shan
Yen, Men‐Luh
Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions
title Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions
title_full Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions
title_fullStr Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions
title_full_unstemmed Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions
title_short Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions
title_sort oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing sirt1 functions
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783884/
https://www.ncbi.nlm.nih.gov/pubmed/28975701
http://dx.doi.org/10.1111/jcmm.13356
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