Dasatinib and Quercetin Senolytic Treatment Delays Early Onset Intervertebral Disc Degeneration in SM/J Mice

Authors

• Emanuel J. Novais, Thomas Jefferson UniversityFollow
• Olivia K. Ottone, Thomas Jefferson UniversityFollow
• Sanjana Jagannath, Thomas Jefferson UniversityFollow
• Esther Jesutofunmi AkandeFollow
• Makarand V. Risbud, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

4-14-2026

Comments

This article is the author's final published version in Bone Research, Volume 14, Issue 1, 2026, Article number 42.

The published version is available at https://doi.org/10.1038/s41413-026-00526-4. Copyright © The Author(s) 2026.

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 or senescence status, DQ-treated mice showed lower grades of degeneration and a decreased abundance of senescence markers, including p19ARF, p21, and the senescence-associated secretory phenotype (SASP). DQ improved disc cell viability and phenotype retention and retarded fibrosis of the nucleus pulposus tissue. Transcriptomic analysis revealed tissue-specific effects of the treatment, with cell cycle regulation and JNK signaling being commonly affected across different tissue types. A comparison of SM/J data with DQ-mediated aging-dependent amelioration of disc degeneration in C57BL/6 N mice identified Junb and Zfp36l1 signaling as shared DQ targets in the mouse disc. Notably, the in vitro inhibition studies of the JUN pathway in human degenerated NP cells mimicked the benefits of DQ, namely, a reduction in senescence and SASP. This study reinforces the efficacy of senolytic treatment in ameliorating local senescence and intervertebral disc fibrosis.

Recommended Citation

Novais, Emanuel J.; Ottone, Olivia K.; Jagannath, Sanjana; Akande, Esther Jesutofunmi; and Risbud, Makarand V., "Dasatinib and Quercetin Senolytic Treatment Delays Early Onset Intervertebral Disc Degeneration in SM/J Mice" (2026). Department of Orthopaedic Surgery Faculty Papers. Paper 270.
https://jdc.jefferson.edu/orthofp/270

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Language

English