ArticleThe Journal of clinical investigation2024
Disassembly of the TRIM56-ATR complex promotes cytoDNA/cGAS/STING axis-dependent intervertebral disc inflammatory degeneration.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Therapeutic effects of stem cell-derived extracellular vesicles in animal models of intervertebral disc degeneration: a systematic review and meta-analysis of species differences and delivery strategies.Frontiers in bioengineering and biotechnology · 2026Pooled it
- A Dual-Functional Nanoplatform Targeting the dsDNA-cGAS Axis to Mitigate Disc Degeneration and Aberrant Innervation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MnOMaterials today. Bio · 2026Article
- D-allose reprogrammes the mitophagy-mtDNA-cGAS-STING-ADM2 axis to restore nucleus pulposus cell homeostasis in intervertebral disc degeneration.Experimental & molecular medicine · 2026Article
- HDAC1 maintains metabolic homeostasis in nucleus pulposus cells via post-translational modification interactions with YBX1.Experimental & molecular medicine · 2026Article
- TRIM25 facilitates mitochondrial dysfunction and extracellular matrix degradation by enhancing USP7-driven ENO1 deubiquitination during intervertebral disc degeneration.Clinical and translational medicine · 2026Article
- Lysosomal Dysfunction Is Associated With Intervertebral Disc Degeneration: Multiomics and Machine Learning Identify Molecular Subtypes and Hub Genes.The journal of gene medicine · 2026Article
- SenFlag gene signature identifies senescent cells in mouse and human tissues through a conserved core transcriptional program.The EMBO journal · 2026Article
- Review
- Biomimetic nanoplatforms modulating mitochondrial pathways in IVDD.Journal of nanobiotechnology · 2026Article
- Microenvironment-educated MSC-EVs loaded injectable smart hydrogel for targeting senescent nucleus pulposus cells and inhibiting ferroptosis against intervertebral disc degeneration.Bioactive materials · 2026Article
- Calming sterile inflammation in intervertebral disc degeneration: taurine disrupts mitochondria-cGAS-STING signaling via autophagy enhancement.Precision clinical medicine · 2026Article
- A continuous DNA repairing system for alleviating intervertebral disc degeneration.Journal of nanobiotechnology · 2026Article
- ROS-responsive hydrogel microspheres deliver shTMEM2-loaded liposomes to suppress pyroptosis and ameliorate intervertebral disc degeneration.Journal of nanobiotechnology · 2026Article
- Elevated TRIM25 Impairs Poly (ADP-ribose) Metabolism via PARG Degradation and Mediates Compression-Induced Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A ROS and pH dual - responsive hydrogel-nanoparticle system restores intervertebral disc and alleviates related pain by modulating senescence and panoptosis of nucleus pulposus cells.Materials today. Bio · 2026Article
- Ubiquitination-mediated PRDX2 alleviates intervertebral disc degeneration via restraining TBHP-induced nucleus pulposus cell apoptosis, ferroptosis and ECM degradation.Journal of inflammation (London, England) · 2026Article
- Albiflorin Relieves Intervertebral Disc Degeneration Through Inhibiting Nucleus Pulposus Cell via the p38 MAPK/NF-κB Pathway.Immunity, inflammation and disease · 2026Article
- Plasma Proteomic Profiling Identifies a Six-Protein Panel for Grading and Predicting Intervertebral Disc Degeneration.Journal of proteome research · 2026Article
- Roles and Mechanisms of TRIM Family Proteins in Inflammation in the Brain and Beyond.International journal of molecular sciences · 2026Review
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socioeconomic challenge to the aging population and is largely attributed to intervertebral disc degeneration (IVDD). Elastic nucleus pulposus (NP) tissue is essential for the maintenance of IVD structural and functional integrity. The accumulation of senescent NP cells with an inflammatory hypersecretory phenotype due to aging and other damaging factors is a distinctive hallmark of IVDD initiation and progression. In this study, we reveal a mechanism of IVDD progression in which aberrant genomic DNA damage promoted NP cell inflammatory senescence via activation of the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) axis but not of absent in melanoma 2 (AIM2) inflammasome assembly. Ataxia-telangiectasia-mutated and Rad3-related protein (ATR) deficiency destroyed genomic integrity and led to cytosolic mislocalization of genomic DNA, which acted as a powerful driver of cGAS/STING axis-dependent inflammatory phenotype acquisition during NP cell senescence. Mechanistically, disassembly of the ATR-tripartite motif-containing 56 (ATR-TRIM56) complex with the enzymatic liberation of ubiquitin-specific peptidase 5 (USP5) and TRIM25 drove changes in ATR ubiquitination, with ATR switching from K63- to K48-linked modification, c thereby promoting ubiquitin-proteasome-dependent dynamic instability of ATR protein during NP cell senescence progression. Importantly, an engineered extracellular vesicle-based strategy for delivering ATR-overexpressing plasmid cargo efficiently diminished DNA damage-associated NP cell senescence and substantially mitigated IVDD progression, indicating promising targets and effective approaches to ameliorate the chronic pain and disabling effects of IVDD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.