Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients

• Published in: Biomedicines Vol. 11; no. 7; p. 1994
• Main Authors: 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
• Format: Journal Article Web Resource
• Language: English
• Published: Switzerland MDPI AG 14-07-2023; Multidisciplinary Digital Publishing Institute (MDPI); MDPI
• Subjects: Age; Biochemistry, Genetics and Molecular Biology (all); Biological response modifiers; Biotechnology industry; Book publishing; Brief Report; Cell fate; Cell self-renewal; Chondrocytes; Comparative analysis; Development and progression; Gene expression; General Biochemistry, Genetics and Molecular Biology; Genes; Genotype & phenotype; Human health sciences; Inflammation; Interferon; Medical innovations; Medical research; Medicine (miscellaneous); Medicine, Experimental; Microenvironments; MSC; Osteoarthritis; Rheumatology; Rhumatologie; Sciences de la santé humaine; Senescence; Software; Stem cells; Synoviocytes; Transforming growth factor-b1; Transforming growth factors; Variance analysis; γ-Interferon; France; United States; United States > US; Germany; senescence; MSC; osteoarthritis
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11071994

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.