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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/7/1994 |
| _version_ | 1797590172083159040 |
|---|---|
| author | Giuseppe Fusi Michael Constantinides Christina Fissoun Lydiane Pichard Yves-Marie Pers Rosanna Ferreira-Lopez Veronique Pantesco Christophe Poulet Olivier Malaise Dominique De Seny Jean-Marc Lemaitre Christian Jorgensen Jean-Marc Brondello |
| author_facet | Giuseppe Fusi Michael Constantinides Christina Fissoun Lydiane Pichard Yves-Marie Pers Rosanna Ferreira-Lopez Veronique Pantesco Christophe Poulet Olivier Malaise Dominique De Seny Jean-Marc Lemaitre Christian Jorgensen Jean-Marc Brondello |
| author_sort | Giuseppe Fusi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T01:16:43Z |
| format | Article |
| id | doaj.art-821ba450a9aa49e8a33748357f4bf3d1 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T01:16:43Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-821ba450a9aa49e8a33748357f4bf3d12023-11-18T18:27:56ZengMDPI AGBiomedicines2227-90592023-07-01117199410.3390/biomedicines11071994Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic PatientsGiuseppe Fusi0Michael Constantinides1Christina Fissoun2Lydiane Pichard3Yves-Marie Pers4Rosanna Ferreira-Lopez5Veronique Pantesco6Christophe Poulet7Olivier Malaise8Dominique De Seny9Jean-Marc Lemaitre10Christian Jorgensen11Jean-Marc Brondello12IRMB, University Montpellier, INSERM, 34295 Montpellier, FranceIRMB, University Montpellier, INSERM, 34295 Montpellier, FranceIRMB, University Montpellier, INSERM, 34295 Montpellier, FranceSAFE-iPSC Facility INGESTEM, Montpellier University Hospital, 34298 Montpellier, FranceIRMB, University Montpellier, INSERM, 34295 Montpellier, FranceIRMB, University Montpellier, INSERM, 34295 Montpellier, FranceIRMB, University Montpellier, INSERM, 34295 Montpellier, FranceLaboratory and Service of Rheumatology, GIGA-I3, Université de Liège, 4000 Liege, BelgiumLaboratory and Service of Rheumatology, GIGA-I3, Université de Liège, 4000 Liege, BelgiumLaboratory and Service of Rheumatology, GIGA-I3, Université de Liège, 4000 Liege, BelgiumIRMB, University Montpellier, INSERM, 34295 Montpellier, FranceIRMB, University Montpellier, INSERM, 34295 Montpellier, FranceIRMB, University Montpellier, INSERM, 34295 Montpellier, FranceSenescent 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.https://www.mdpi.com/2227-9059/11/7/1994senescenceMSCosteoarthritis |
| spellingShingle | Giuseppe Fusi Michael Constantinides Christina Fissoun Lydiane Pichard Yves-Marie Pers Rosanna Ferreira-Lopez Veronique Pantesco Christophe Poulet Olivier Malaise Dominique De Seny Jean-Marc Lemaitre Christian Jorgensen Jean-Marc Brondello Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients Biomedicines senescence MSC osteoarthritis |
| 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 | senescence MSC osteoarthritis |
| url | https://www.mdpi.com/2227-9059/11/7/1994 |
| work_keys_str_mv | AT giuseppefusi senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT michaelconstantinides senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT christinafissoun senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT lydianepichard senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT yvesmariepers senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT rosannaferreiralopez senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT veroniquepantesco senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT christophepoulet senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT oliviermalaise senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT dominiquedeseny senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT jeanmarclemaitre senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT christianjorgensen senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients AT jeanmarcbrondello senescencedriveninflammatoryandtrophicmicroenvironmentimprintsmesenchymalstromalstemcellsinosteoarthriticpatients |