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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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