The Triterpenoid Nrf2 Activator, CDDO-Me, Decreases Neutrophil Senescence in a Murine Model of Joint Damage
Abstract
:1. Introduction
2. Results
2.1. Effect of CDDO-Me on Caspase-Mediated Apoptosis Measured by Poly [ADP-Ribose] Polymerase 1 (PARP-1) Cleavage and on Cell Necrosis in Late Cultures
2.2. CDDO-Me Increases Nrf2 Levels, and Decreases Surface CXCR4 Expression and p38 Mitogen-Activated Protein Kinase (MAPK) Phosphorylation in BM-Derived Neutrophils
2.3. CDDO-Me Effects Neutrophil Senescence
2.4. CDDO-Me Inhibits Disease Activity and MMP-9 and TNF-α Production in Synovial Tissue Extracts
2.5. Correlation between Disease Activity in CIOA Mice and CXCR4 Expression on BM-Derived Ly6G+ Neutrophils
2.6. Effect of CDDO-Me on Blood-and BM-Neutrophil Pools in CIOA Mice and on Nrf2 Intracellular Level in CIOA Neutrophils
3. Discussion
4. Materials and Methods
4.1. Chemical Compound
4.2. Animals
4.3. Model of Collagenase-Induced Osteoarthritis (CIOA) and Treatment
4.4. Histology
4.5. Synovial Tissue Extracts
4.6. Enzyme-Linked Immunosorbent Assay (ELISA)
4.7. Cell Isolation and Purification
4.8. Analysis of PARP-1 Cleavage
4.9. In Vitro Chemotaxis Assay towards SDF-1
4.10. Flow Cytometry for Phenotyping Cell Surface Expression of Neutrophil Receptors and Necrosis
4.11. Flow Cytometry for Intracellular Detection of Nrf2, Phosphorylated p38, and β-Galactosidase
4.12. Flow Cytometry Data Analysis
4.13. Immunofluorescence for Detection of β-Galactosidase and CXCR4
4.14. Determination of β-Galactosidase Activity
4.15. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Amirova, K.M.; Dimitrova, P.A.; Leseva, M.N.; Koycheva, I.K.; Dinkova-Kostova, A.T.; Georgiev, M.I. The Triterpenoid Nrf2 Activator, CDDO-Me, Decreases Neutrophil Senescence in a Murine Model of Joint Damage. Int. J. Mol. Sci. 2023, 24, 8775. https://doi.org/10.3390/ijms24108775
Amirova KM, Dimitrova PA, Leseva MN, Koycheva IK, Dinkova-Kostova AT, Georgiev MI. The Triterpenoid Nrf2 Activator, CDDO-Me, Decreases Neutrophil Senescence in a Murine Model of Joint Damage. International Journal of Molecular Sciences. 2023; 24(10):8775. https://doi.org/10.3390/ijms24108775
Chicago/Turabian StyleAmirova, Kristiana M., Petya A. Dimitrova, Milena N. Leseva, Ivanka K. Koycheva, Albena T. Dinkova-Kostova, and Milen I. Georgiev. 2023. "The Triterpenoid Nrf2 Activator, CDDO-Me, Decreases Neutrophil Senescence in a Murine Model of Joint Damage" International Journal of Molecular Sciences 24, no. 10: 8775. https://doi.org/10.3390/ijms24108775