Dasatinib and quercetin senolytic treatment delays progression of disc degeneration in SM/J mice

ABSTRACT: Genetic background is a major determinant of disc degeneration, a leading cause of chronic back pain and disability. Herein, we demonstrate that premature disc cell senescence contributes to early-onset degeneration in SM/J mice and test two systemic senotherapeutic strategies to mitigate it: Navitoclax (Nav.) and a cocktail of Dasatinib and Quercetin (DQ). While Nav. treatment did not improve severe degeneration in SM/J mice, DQ-treated mice showed lower grades of degeneration and decreased levels of senescence markers p19ARF and p21. DQ promoted disc cell viability, phenotype retention, and limited fibrotic remodeling of the NP tissue. Transcriptomic analysis showed disc compartment-specific effects of the treatment, but cell cycle regulation and JNK signaling were commonly affected across tissue types. Additionally, comparison with previously reported C57BL/6N mice treated with DQ identified Junb and Zfp36l1 signaling as targets of DQ ameliorating intervertebral disc degeneration in mice. This study reinforces the positive role of senolytic treatments in mediating local senescence and intervertebral disc fibrosis. Moreover, these findings suggest that Junb and Zfp36l1 are mediators of this effect.

ORGANISM(S): Mus musculus

PROVIDER: GSE281300 | GEO | 2026/04/22

REPOSITORIES: GEO