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Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients
Senescent cells promote progressive tissue degeneration through the establishment of a combined inflammatory and trophic microenvironment. The cellular senescence state has therefore emerged as a central driving mechanism of numerous age-related diseases, including osteoarthritis (OA), the most comm...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377055/ https://www.ncbi.nlm.nih.gov/pubmed/37509633 http://dx.doi.org/10.3390/biomedicines11071994 |
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author | Fusi, Giuseppe Constantinides, Michael Fissoun, Christina Pichard, Lydiane Pers, Yves-Marie Ferreira-Lopez, Rosanna Pantesco, Veronique Poulet, Christophe Malaise, Olivier De Seny, Dominique Lemaitre, Jean-Marc Jorgensen, Christian Brondello, Jean-Marc |
author_facet | Fusi, Giuseppe Constantinides, Michael Fissoun, Christina Pichard, Lydiane Pers, Yves-Marie Ferreira-Lopez, Rosanna Pantesco, Veronique Poulet, Christophe Malaise, Olivier De Seny, Dominique Lemaitre, Jean-Marc Jorgensen, Christian Brondello, Jean-Marc |
author_sort | Fusi, Giuseppe |
collection | PubMed |
description | Senescent cells promote progressive tissue degeneration through the establishment of a combined inflammatory and trophic microenvironment. The cellular senescence state has therefore emerged as a central driving mechanism of numerous age-related diseases, including osteoarthritis (OA), the most common rheumatic disease. Senescence hallmarks are detectable in chondrocytes, synoviocytes and sub-chondral bone cells. This study investigates how the senescence-driven microenvironment could impact the cell fate of resident osteoarticular mesenchymal stromal/stem cells (MSCs) that are hence contributing to OA disease progression. For that purpose, we performed a comparative gene expression analysis of MSCs isolated from healthy donors that were in vitro chronically exposed either to interferon-gamma (IFN-γ) or Transforming Growth Factor beta 1 (TGFβ1), two archetypical factors produced by senescent cells. Both treatments reduced MSC self-renewal capacities by upregulating different senescence-driven cycle-dependent kinase inhibitors. Furthermore, a common set of differentially expressed genes was identified in both treated MSCs that was also found enriched in MSCs isolated from OA patients. These findings highlight an imprinting of OA MSCs by the senescent joint microenvironment that changes their matrisome gene expression. Altogether, this research gives new insights into OA etiology and points to new innovative therapeutic opportunities to treat OA patients. |
format | Online Article Text |
id | pubmed-10377055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103770552023-07-29 Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients Fusi, Giuseppe Constantinides, Michael Fissoun, Christina Pichard, Lydiane Pers, Yves-Marie Ferreira-Lopez, Rosanna Pantesco, Veronique Poulet, Christophe Malaise, Olivier De Seny, Dominique Lemaitre, Jean-Marc Jorgensen, Christian Brondello, Jean-Marc Biomedicines Brief Report Senescent cells promote progressive tissue degeneration through the establishment of a combined inflammatory and trophic microenvironment. The cellular senescence state has therefore emerged as a central driving mechanism of numerous age-related diseases, including osteoarthritis (OA), the most common rheumatic disease. Senescence hallmarks are detectable in chondrocytes, synoviocytes and sub-chondral bone cells. This study investigates how the senescence-driven microenvironment could impact the cell fate of resident osteoarticular mesenchymal stromal/stem cells (MSCs) that are hence contributing to OA disease progression. For that purpose, we performed a comparative gene expression analysis of MSCs isolated from healthy donors that were in vitro chronically exposed either to interferon-gamma (IFN-γ) or Transforming Growth Factor beta 1 (TGFβ1), two archetypical factors produced by senescent cells. Both treatments reduced MSC self-renewal capacities by upregulating different senescence-driven cycle-dependent kinase inhibitors. Furthermore, a common set of differentially expressed genes was identified in both treated MSCs that was also found enriched in MSCs isolated from OA patients. These findings highlight an imprinting of OA MSCs by the senescent joint microenvironment that changes their matrisome gene expression. Altogether, this research gives new insights into OA etiology and points to new innovative therapeutic opportunities to treat OA patients. MDPI 2023-07-14 /pmc/articles/PMC10377055/ /pubmed/37509633 http://dx.doi.org/10.3390/biomedicines11071994 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Report Fusi, Giuseppe Constantinides, Michael Fissoun, Christina Pichard, Lydiane Pers, Yves-Marie Ferreira-Lopez, Rosanna Pantesco, Veronique Poulet, Christophe Malaise, Olivier De Seny, Dominique Lemaitre, Jean-Marc Jorgensen, Christian Brondello, Jean-Marc Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients |
title | Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients |
title_full | Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients |
title_fullStr | Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients |
title_full_unstemmed | Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients |
title_short | Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients |
title_sort | senescence-driven inflammatory and trophic microenvironment imprints mesenchymal stromal/stem cells in osteoarthritic patients |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377055/ https://www.ncbi.nlm.nih.gov/pubmed/37509633 http://dx.doi.org/10.3390/biomedicines11071994 |
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