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Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis
BACKGROUND: Articular injection of mesenchymal stem cells (MSCs) has been applied to treat knee osteoarthritis (kOA), but its clinical outcomes are controversial. This study investigated whether an articular inflammatory microenvironment (AIM) impacts MSC-based therapy in a rat model of kOA. METHODS...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280917/ https://www.ncbi.nlm.nih.gov/pubmed/37337188 http://dx.doi.org/10.1186/s12916-023-02923-6 |
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author | Fan, Mengqiang Tong, Peijian Yan, Li Li, Ting Ren, Jiadan Huang, Jiefeng Du, Wenxi Zhou, Li Shan, Letian |
author_facet | Fan, Mengqiang Tong, Peijian Yan, Li Li, Ting Ren, Jiadan Huang, Jiefeng Du, Wenxi Zhou, Li Shan, Letian |
author_sort | Fan, Mengqiang |
collection | PubMed |
description | BACKGROUND: Articular injection of mesenchymal stem cells (MSCs) has been applied to treat knee osteoarthritis (kOA), but its clinical outcomes are controversial. This study investigated whether an articular inflammatory microenvironment (AIM) impacts MSC-based therapy in a rat model of kOA. METHODS: The biological change of MSCs and the functional change of MSCs on chondrocytes were evaluated under AIM. The key mediator and mechanism for the AIM impact on MSC therapy were explored via gain- and loss-of-function approaches. RESULTS: The results showed that MSCs exerted potent anti-kOA effects in vivo and in vitro, but that this therapy become chondrodestructive if a chronic AIM was present. Mechanistically, the overexpression of MMP13 in the injected MSCs via a MAPKs-AP1 signaling axis was revealed as the underlying mechanism for the detriment outcome. CONCLUSIONS: This study thus clarifies recent clinical findings while also suggesting a means to overcome any detrimental effects of MSC-based therapy while improving its efficacy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-023-02923-6. |
format | Online Article Text |
id | pubmed-10280917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-102809172023-06-21 Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis Fan, Mengqiang Tong, Peijian Yan, Li Li, Ting Ren, Jiadan Huang, Jiefeng Du, Wenxi Zhou, Li Shan, Letian BMC Med Research Article BACKGROUND: Articular injection of mesenchymal stem cells (MSCs) has been applied to treat knee osteoarthritis (kOA), but its clinical outcomes are controversial. This study investigated whether an articular inflammatory microenvironment (AIM) impacts MSC-based therapy in a rat model of kOA. METHODS: The biological change of MSCs and the functional change of MSCs on chondrocytes were evaluated under AIM. The key mediator and mechanism for the AIM impact on MSC therapy were explored via gain- and loss-of-function approaches. RESULTS: The results showed that MSCs exerted potent anti-kOA effects in vivo and in vitro, but that this therapy become chondrodestructive if a chronic AIM was present. Mechanistically, the overexpression of MMP13 in the injected MSCs via a MAPKs-AP1 signaling axis was revealed as the underlying mechanism for the detriment outcome. CONCLUSIONS: This study thus clarifies recent clinical findings while also suggesting a means to overcome any detrimental effects of MSC-based therapy while improving its efficacy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-023-02923-6. BioMed Central 2023-06-19 /pmc/articles/PMC10280917/ /pubmed/37337188 http://dx.doi.org/10.1186/s12916-023-02923-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Fan, Mengqiang Tong, Peijian Yan, Li Li, Ting Ren, Jiadan Huang, Jiefeng Du, Wenxi Zhou, Li Shan, Letian Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis |
title | Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis |
title_full | Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis |
title_fullStr | Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis |
title_full_unstemmed | Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis |
title_short | Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis |
title_sort | detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280917/ https://www.ncbi.nlm.nih.gov/pubmed/37337188 http://dx.doi.org/10.1186/s12916-023-02923-6 |
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