ArticleExperimental & molecular medicine2022
Cytosolic escape of mitochondrial DNA triggers cGAS-STING-NLRP3 axis-dependent nucleus pulposus cell pyroptosis.
Article in Experimental & molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers.
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182 citing papers in PubMed, 298 citations in OpenAlex.
- A nucleic acid regulation strategy under mechanical stress for intervertebral disc degeneration treatment.Bioactive materials · 2026Article
- Molecular Basis of Ferroptosis and Pyroptosis in Lead-Induced Neurotoxicity: A Narrative Review of Current Evidence and Therapeutic Implications.Biological trace element research · 2026Review
- Closed-Loop Neuromodulation for Brain Fatigue: From Real-Time Biomarkers to Adaptive Intervention.International journal of molecular sciences · 2026Review
- Mitochondrial DNA leakage in oocytes activates cGAS-STING signaling to drive ovarian aging.Nature aging · 2026Article
- Macrophage immunometabolic reprogramming in inflammatory repair failure in osteonecrosis of the femoral head.Journal of orthopaedic translation · 2026Review
- Senkyunolide I Inhibits mtDNA-cGAS-STING Signaling in Macrophages via Targeting VDAC1 Oligomerization to Attenuate Ulcerative Colitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Innate immune crosstalk in ALS/FTD pathogenesis.Cell insight · 2026Review
- Itgb1-Mediated Stabilization of Vimentin Alleviates Excessive Mechanical Stress-Induced Nucleus Pulposus Cell Pyroptosis and Intervertebral Disc Degeneration via PINK1-Parkin-Dependent Mitophagy.Cell proliferation · 2026Article
- Biomimetic nanoplatforms modulating mitochondrial pathways in IVDD.Journal of nanobiotechnology · 2026Article
- Intratumoral bicarbonate functions as an adjuvant to potentiate PD-1 blockade in hepatocellular carcinoma.Oncogene · 2026Article
- From energy metabolic homeostasis to immune remodeling: the role and therapeutic potential of STING signaling in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer's disease pathogenesis.Neuron · 2026Article
- Mitochondria as convergence hubs for innate immunity pathways.Communications biology · 2026Review
- Inhibition of STING pathway attenuates experimental abdominal aortic aneurysm progression.Acta pharmacologica Sinica · 2026Article
- Notch signaling-targeted biomimetic hydrogel constructs an anti-inflammatory "flood-control" system to alleviate pyroptosis for intervertebral disc degeneration treatment.Materials today. Bio · 2026Article
- Calming sterile inflammation in intervertebral disc degeneration: taurine disrupts mitochondria-cGAS-STING signaling via autophagy enhancement.Precision clinical medicine · 2026Article
- Melatonin alleviates neuroinflammation in ischemic stroke by regulating cyclic GMP-AMP synthase- mediated microglial pyroptosis signaling.Neural regeneration research · 2026Article
- Subthreshold Thermal Stress Aggravates Methamphetamine-Induced Cardiomyocyte Pyroptosis via the Mitochondrial ROS/BAX/mtDNA/NLRP3 Pathway.International journal of molecular sciences · 2026Article
- A continuous DNA repairing system for alleviating intervertebral disc degeneration.Journal of nanobiotechnology · 2026Article
- Mitochondrial Metabolic Reprogramming in Colorectal Cancer-Associated Fibroblasts: An Up-to-Date Review.Cancers · 2026Review
122 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 1 institution in 1 country.
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Abstract
Low back pain (LBP) is a major musculoskeletal disorder and the socioeconomic problem with a high prevalence that mainly involves intervertebral disc (IVD) degeneration, characterized by progressive nucleus pulposus (NP) cell death and the development of an inflammatory microenvironment in NP tissue. Excessively accumulated cytosolic DNA acts as a damage-associated molecular pattern (DAMP) that is monitored by the cGAS-STING axis to trigger the immune response in many degenerative diseases. NLRP3 inflammasome-dependent pyroptosis is a type of inflammatory programmed death that promotes a chronic inflammatory response and tissue degeneration. However, the relationship between the cGAS-STING axis and NLRP3 inflammasome-induced pyroptosis in the pathogenesis of IVD degeneration remains unclear. Here, we used magnetic resonance imaging (MRI) and histopathology to demonstrate that cGAS, STING, and NLRP3 are associated with the degree of IVD degeneration. Oxidative stress induced cGAS-STING axis activation and NLRP3 inflammasome-mediated pyroptosis in a STING-dependent manner in human NP cells. Interestingly, the canonical morphological and functional characteristics of mitochondrial permeability transition pore (mPTP) opening with the cytosolic escape of mitochondrial DNA (mtDNA) were observed in human NP cells under oxidative stress. Furthermore, the administration of a specific pharmacological inhibitor of mPTP and self-mtDNA cytosolic leakage effectively reduced NLRP3 inflammasome-mediated pyroptotic NP cell death and microenvironmental inflammation in vitro and degenerative progression in a rat disc needle puncture model. Collectively, these data highlight the critical roles of the cGAS-STING-NLRP3 axis and pyroptosis in the progression of IVD degeneration and provide promising therapeutic approaches for discogenic LBP.
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