Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice.

Autor: Novais EJ; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, USA.; Graduate Program in Cell Biology and Regenerative Medicine, Jefferson College of Life Sciences, Thomas Jefferson University, Philadelphia, USA.; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal., Tran VA; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, USA., Johnston SN; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, USA.; Graduate Program in Cell Biology and Regenerative Medicine, Jefferson College of Life Sciences, Thomas Jefferson University, Philadelphia, USA., Darris KR; Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.; Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, and North Carolina State University, Raleigh, NC, USA., Roupas AJ; Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.; Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, and North Carolina State University, Raleigh, NC, USA., Sessions GA; Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.; Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, and North Carolina State University, Raleigh, NC, USA., Shapiro IM; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, USA.; Graduate Program in Cell Biology and Regenerative Medicine, Jefferson College of Life Sciences, Thomas Jefferson University, Philadelphia, USA., Diekman BO; Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.; Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, and North Carolina State University, Raleigh, NC, USA., Risbud MV; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, USA. makarand.Risbud@jefferson.edu.; Graduate Program in Cell Biology and Regenerative Medicine, Jefferson College of Life Sciences, Thomas Jefferson University, Philadelphia, USA. makarand.Risbud@jefferson.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Sep 03; Vol. 12 (1), pp. 5213. Date of Electronic Publication: 2021 Sep 03.
DOI: 10.1038/s41467-021-25453-2
Abstrakt: Intervertebral disc degeneration is highly prevalent within the elderly population and is a leading cause of chronic back pain and disability. Due to the link between disc degeneration and senescence, we explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice. We treated C57BL/6 mice beginning at 6, 14, and 18 months of age, and analyzed them at 23 months of age. Interestingly, 6- and 14-month D + Q cohorts show lower incidences of degeneration, and the treatment results in a significant decrease in senescence markers p16 INK4a , p19 ARF , and SASP molecules IL-6 and MMP13. Treatment also preserves cell viability, phenotype, and matrix content. Although transcriptomic analysis shows disc compartment-specific effects of the treatment, cell death and cytokine response pathways are commonly modulated across tissue types. Results suggest that senolytics may provide an attractive strategy to mitigating age-dependent disc degeneration.
(© 2021. The Author(s).)
Databáze: MEDLINE
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