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SIRT6 loss causes intervertebral disc degeneration in mice by dysregulating senescence and SASP status

ABSTRACT: SIRT6 loss causes intervertebral disc degeneration in mice by dysregulating senescence and SASP status

PROVIDER: PRJNA1157379 | ENA |

REPOSITORIES: ENA

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SIRT6 loss causes intervertebral disc degeneration in mice by dysregulating senescence and SASP status

Project description:Transcriptional analysis of 24-month-old primary nucleus pulposus (NP) and annulus fibrosus (AF) mouse disc tissues from Sirt6fl/fl and Sirt6cKO mice, which harbor a mutation which constiuitively deletes Sirtuin 6 in aggrecan expressing cells. SIRT6 loss causes intervertebral disc degeneration in mice by dysregulating senescence and SASP status

2024-10-02 | GSE276439 | GEO

The STING pathway does not contribute to the onset of cell senescence and SASP induction in the intervertebral disc

Project description:Transcriptional analysis of 6-month-old primary nucleus pulposus (NP) and annulus fibrosus (AF) mouse disc tissues from wild-type (WT) and N153S mice, which harbor a mutation wich constiuitively activates Sting. Mouse details available here: https://www.jax.org/strain/033543 The cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP), which is associated with intervertebral disc degeneration, and has had implications in inflammatory musculoskeletal disorders. We examined the role of STING in the disc by examining the transcriptomic profiles of nucleus pulposus and annulus fibrosus cells in WT and N153S mice using microarray.

2022-07-06 | GSE188909 | GEO

Intervertebral disc degeneration

Project description:Intervertebral disc degeneration

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Proteomics for patients with intervertebral disc degeneration

Project description:Proteomics for patients with intervertebral disc degeneration

2024-04-10 | PXD051351 |

Adam8Mutant vs DBA intervertebral disc injury

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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

Can Scoliotic Discs be Controls for Molecular Studies in Intervertebral Disc Research?- Insights from Proteomics.

Project description:Research on disc degeneration has been heterogeneous in their use of control discs used for comparison with diseased discs. Discs from scoliosis, cadavers and voluntary organ donors are the common controls used in intervertebral disc research. In order to find out the ideal control among these discs, the characters of scoliotic discs and discs from MRI normal voluntary organ donors controls used in disc research has been analysed using proteomics and to establish 'True Controls' that can be utilized for future Intervertebral disc (IVD) research.

2022-06-09 | PXD018968 | Pride

Nucleus pulposus related lncRNA and mRNA expression profiles in intervertebral disc degeneration

Project description:Intervertebral disc degeneration (IDD) leads to low back pain and disability globally. The pathophysiology of IDD is not entirely understood. There is increasing evidence that long noncoding RNAs (lncRNAs) play a key regulatory role in a wide range of biological processes. The purpose of this study was to comprehensively lncRNA and mRNA expression profiles of human intervertebral disc (IVD) tissues, specifically nucleus pulpous (NP) tissues, with early and advanced stages of disc degeneration. The overview of lncRNA and mRNA expression profiles in the current study revealed that differentially expressed lncRNAs and mRNAs were identified that have been reported to be relevant to IDD. Importantly, differentially expressed lncRNAs and mRNAs that regulate the major signaling pathways, such as NF-κB, MAPK, and Wnt signaling, that are well known to be responsible for the pathogenesis of IDD.

2023-02-09 | GSE186542 | GEO

Oral Citrate Supplementation Mitigates Age-Associated Pathological Intervertebral Disc Calcification in LG/J Mice

Project description:Despite the high prevalence of age-dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. Here, we investigate the efficacy of long-term oral K3Citrate supplementation in ameliorating disc calcification in LG/J mice, a model of spontaneous age-associated disc calcification. K3Citrate successfully reduced the incidence of disc calcification in LG/J mice without deleterious effects on vertebral bone structure, plasma chemistry, and locomotion. Notably, a positive effect on grip strength, a marker of frailty, was evident in treated mice. Spectroscopic investigation of the persisting calcified nodules indicated K3Citrate did not alter the mineral composition, and collagen 10 and aggrecan staining revealed that reactivation of an endochondral differentiation program in endplates may drive LG/J disc calcification. Importantly, K3Citrate reduced calcification incidence without altering the abundance of endplate hypertrophic chondrocytes, suggesting mitigation of disc calcification through Ca2+ chelation. This was further supported by the inability of K3Citrate to inhibit hypertrophic differentiation of chondrogenic ATDC5 cells and minimal effects on their metabolic status. Overall, this study sheds light on the pathogenesis of intervertebral disc calcification in LG/J mice and underscores the therapeutic potential of K3Citrate as a systemic intervention strategy for disc calcification.

2024-08-16 | GSE270561 | GEO

Proteomic Signature of Nucleus Pulposus of Human Intervertebral Disc

Project description:Intervertebral Disc (IVD) degeneration leading to Low back pain (LBP) is the most common musculoskeletal disorder. Lack of knowledge on the intricate homeostatic mechanisms necessitates proteomic characterisation of a normal human IVD to understand the biological process and unravel the pathomechanisms of degenerative disc disease (DDD). In this study, we employed proteomic approach coupled with tandem mass-spectrometry to derive the comprehensive list of proteins expressed in true biologically normal control discs. This would serve as the basis for identifying the interacting molecules participating in significant biological processes and pathways disrupted during aging and degeneration.

2021-09-09 | PXD016560 | Pride

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