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

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

PROVIDER: PRJNA646873 | ENA |

REPOSITORIES: ENA

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

Project description:Intervertebral disc degeneration is highly prevalent in the elderly population and is a leading cause of chronic back pain and disability. Studies have linked degenration with increased disc cell senescence. Likewise, senolytics such as Dasatinib + Quercetin combination may provide a novel approach to mitigate age-dependnt disc degeneration. We used microarrays to explore the transcriptomics of differentially expressed genes between aged disc compartments: AF vs NP at 23M, AF: D+Q vs Veh and NP: D+Q vs Veh.

2021-07-01 | GSE154619 | GEO

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

Project description: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.

2026-04-22 | GSE281300 | GEO

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

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

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Intervertebral disc degeneration

Project description:Intervertebral disc degeneration

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

Project description: Not available

| S-EPMC8417260 | biostudies-literature

Single-cell sequencing data of aged male mice treated with Dasatinib plus Quercetin (DQ)

Project description:Single-cell sequencing data on thymus, bone marrow, liver, muscle and adipose of aged male mice treated with Dasatinib plus Quercetin (DQ)

2026-03-14 | GSE315257 | GEO

Adam8Mutant vs DBA intervertebral disc injury

Project description:Adam8Mutant vs DBA intervertebral disc injury

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Multi-Omics Approach to Elucidate Cerebrospinal Fluid Changes in Dogs with Intervertebral Disc Herniation

Project description:Herniation of the intervertebral disc (IVDH) is the most common cause of neurological and intervertebral disc degeneration-related diseases. Since the disc starts to degenerate before it can be observed by currently available diagnostic methods, there is an urgent need for novel diagnostic approaches. To identify molecular networks and pathways which may play important roles in intervertebral disc herniation, as well as to reveal the potential features which could be useful for monitoring disease progression and prognosis, multi-omics profiling including high-resolution LC-MS-based metabolomics and proteomics was performed. Furthermore, multi-omics data were integrated to decipher a complex interaction between individual omic layers leading to improved prediction model. Together with metabolic pathways related to amino acids and lipid metabolism, and coagulation cascades, our integromics prediction model identified the key features in IVDH, namely the proteins FSTL1, SCG5, NUCB1 and CRSP2 and the metabolites N-acetyl-D-glucosamine and adenine, involved in neuropathic pain, myelination, neurotransmission and inflammatory response, respectively. Their clinical application is to be further investigated. The utilization of novel integrative interdisciplinary strategy may provide opportunities to apply the innovative diagnostic and monitoring methods for degenerative spinal disorders.

2021-11-04 | MTBLS2689 | MetaboLights

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Project description:Proteomics for patients with intervertebral disc degeneration

2024-04-10 | PXD051351 |

Neonatal and Adult Human Intervertebral Disc scRNA-seq

Project description:We report the single-cell RNA-seq (scRNA-seq) data for human neonatal and adult human intervertebral disc (IVD) scRNA-seq. We sequenced cells harvested from three IVDs of a neonatal baby and one IVD from an adult cadaver.

2021-12-07 | GSE189916 | GEO

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