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Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway

Osteoarthritis (OA) is one of the most serious age-related diseases worldwide that drastically affects the quality of life of patients. Despite advancements in the treatment of arthritis, especially with adipose-derived mesenchymal stem cells (ADSCs), senescence-induced alterations in ADSCs negative...

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Autores principales: Li, Zheng, Liu, Lin, Yang, Yanni, Zheng, Haishi, Cai, Yongsong, Ma, Yao, Gu, Ruiying, Xu, Ke, Zhang, Rui, Xu, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187432/
https://www.ncbi.nlm.nih.gov/pubmed/35693701
http://dx.doi.org/10.1155/2022/4620254
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author Li, Zheng
Liu, Lin
Yang, Yanni
Zheng, Haishi
Cai, Yongsong
Ma, Yao
Gu, Ruiying
Xu, Ke
Zhang, Rui
Xu, Peng
author_facet Li, Zheng
Liu, Lin
Yang, Yanni
Zheng, Haishi
Cai, Yongsong
Ma, Yao
Gu, Ruiying
Xu, Ke
Zhang, Rui
Xu, Peng
author_sort Li, Zheng
collection PubMed
description Osteoarthritis (OA) is one of the most serious age-related diseases worldwide that drastically affects the quality of life of patients. Despite advancements in the treatment of arthritis, especially with adipose-derived mesenchymal stem cells (ADSCs), senescence-induced alterations in ADSCs negatively affect the treatment outcomes. This study was aimed at mechanistically exploring whether metformin could ameliorate the senescence of ADSCs and at exploring the effect of metformin-preconditioned ADSCs in an experimental OA mouse model. In this study, an H(2)O(2)-induced mouse ADSC senescent model was established. Cell proliferation, senescence, and autophagy were investigated in vitro. Moreover, the effects of intra-articular injection of metformin-preconditioned ADSCs were investigated in vivo. Metformin could promote autophagy and activate the AMPK/mTOR pathway in ADSCs. The metformin-enhanced autophagy could improve the survival and reduce the senescence of ADSCs. The protective effects of metformin against senescence were partially blocked by 3-methyladenine and compound C. Injection of metformin-preconditioned ADSCs slowed OA progression and reduced OA pain in mice. The results suggest that metformin activates the AMPK/mTOR-dependent autophagy pathway in ADSCs against H(2)O(2)-induced senescence, while metformin-preconditioned ADSCs can potentially inhibit OA progression.
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spelling pubmed-91874322022-06-11 Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway Li, Zheng Liu, Lin Yang, Yanni Zheng, Haishi Cai, Yongsong Ma, Yao Gu, Ruiying Xu, Ke Zhang, Rui Xu, Peng Oxid Med Cell Longev Research Article Osteoarthritis (OA) is one of the most serious age-related diseases worldwide that drastically affects the quality of life of patients. Despite advancements in the treatment of arthritis, especially with adipose-derived mesenchymal stem cells (ADSCs), senescence-induced alterations in ADSCs negatively affect the treatment outcomes. This study was aimed at mechanistically exploring whether metformin could ameliorate the senescence of ADSCs and at exploring the effect of metformin-preconditioned ADSCs in an experimental OA mouse model. In this study, an H(2)O(2)-induced mouse ADSC senescent model was established. Cell proliferation, senescence, and autophagy were investigated in vitro. Moreover, the effects of intra-articular injection of metformin-preconditioned ADSCs were investigated in vivo. Metformin could promote autophagy and activate the AMPK/mTOR pathway in ADSCs. The metformin-enhanced autophagy could improve the survival and reduce the senescence of ADSCs. The protective effects of metformin against senescence were partially blocked by 3-methyladenine and compound C. Injection of metformin-preconditioned ADSCs slowed OA progression and reduced OA pain in mice. The results suggest that metformin activates the AMPK/mTOR-dependent autophagy pathway in ADSCs against H(2)O(2)-induced senescence, while metformin-preconditioned ADSCs can potentially inhibit OA progression. Hindawi 2022-06-03 /pmc/articles/PMC9187432/ /pubmed/35693701 http://dx.doi.org/10.1155/2022/4620254 Text en Copyright © 2022 Zheng Li et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Zheng
Liu, Lin
Yang, Yanni
Zheng, Haishi
Cai, Yongsong
Ma, Yao
Gu, Ruiying
Xu, Ke
Zhang, Rui
Xu, Peng
Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway
title Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway
title_full Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway
title_fullStr Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway
title_full_unstemmed Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway
title_short Metformin Ameliorates Senescence of Adipose-Derived Mesenchymal Stem Cells and Attenuates Osteoarthritis Progression via the AMPK-Dependent Autophagy Pathway
title_sort metformin ameliorates senescence of adipose-derived mesenchymal stem cells and attenuates osteoarthritis progression via the ampk-dependent autophagy pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187432/
https://www.ncbi.nlm.nih.gov/pubmed/35693701
http://dx.doi.org/10.1155/2022/4620254
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