ArticleJournal of translational medicine2023
Mitochondrial DNA induces nucleus pulposus cell pyroptosis via the TLR9-NF-κB-NLRP3 axis.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.Frontiers in immunology · 2026Pooled it
- Management of Musculoskeletal Injuries with an Inflammatory Damage-Associated Molecular Pattern (DAMP) Etiology.Pain and therapy · 2026Review
- PINK1-Parkin pathway-mediated mitophagy in sepsis: friend or foe?Molecular biology reports · 2026Review
- Biomimetic nanoplatforms modulating mitochondrial pathways in IVDD.Journal of nanobiotechnology · 2026Article
- TH5487 specifically targets NLRP3 in FCAS patients resistant to MCC950.Communications biology · 2026Article
- Cyclic tensile loading regulates nucleus pulposus cell autophagy through mitochondrial dynamics: molecular mechanisms and implications.Journal of translational medicine · 2026Review
- Renal-tubular-mitochondrial sequentially targeted nanoagent breaks the vicious cycle of oxidative stress and mtDNA-driven inflammation in acute kidney injury therapy.Journal of nanobiotechnology · 2026Article
- Bidirectional Regulation of NLRP3 Inflammasome and Mitochondrial Quality Control in Sepsis: Mechanisms and Therapeutic Implications.Mediators of inflammation · 2026Review
- Article
- Natural products targeting programmed cell death: a novel therapeutic strategy for intervertebral disc degeneration.International journal of surgery (London, England) · 2026Review
- The Extracellular Matrix and the Immune System in Acute Lung Injury: Partners in Damage and Repair.Biomedicines · 2025Review
- Toward targeting of inflammasome signaling in venous thrombosis.Journal of thrombosis and haemostasis : JTH · 2025Review
- L-theanine-targeted prefrontal cortex improves CUMS-induced depression via the gut-short-chain fatty acids-brain axis.NPJ science of food · 2025Article
- Article
- The Immunogenic Role of Self-DNA in T Cell Immunity.Clinical reviews in allergy & immunology · 2025Review
- From mitochondria to immune networks: new mesenchymal stem cell strategies to treat periodontitis.Stem cell research & therapy · 2025Review
- Acute lung injury: pathogenesis and treatment.Journal of translational medicine · 2025Review
- NLRP3 Inflammasome-Mediated Pyroptosis in Osteoporosis: Osteoimmune Mechanisms and Therapeutic Targeting.Journal of cellular and molecular medicine · 2025Review
- DAMPs cross-talk interpretation of MDD mechanisms.Science advances · 2025Review
- Apoptotic Pathway in Intervertebral Disc Degeneration: From Molecular Pathways to Clinical Interventions.Diagnostics (Basel, Switzerland) · 2025Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNucleus pulposus cell (NPC) death and progressive reduction play important roles in intervertebral disc degeneration (IVDD). As part of a damage-associated molecular pattern, mitochondrial DNA (mtDNA) can be recognized by TLR9 and triggers the expression of NF-κB and NLRP3 inflammasomes, inducing pyroptosis and inflammatory response. However, whether mtDNA induces NPC pyroptosis via the TLR9-NF-κB-NLRP3 axis and promotes IVDD remains uncertain.
methodsWe constructed an in vitro NPC oxidative stress injury model to clarify the mechanism of mtDNA release, TLR9-NF-κB signaling pathway activation, and NPC injury. We further verified the mechanism of action underlying the inhibition of mtDNA release or TLR9 activation in NPC injury in vitro. We then constructed a rat punctured IVDD model to understand the mechanism inhibiting mtDNA release and TLR9 activation in IVDD.
resultsWe used human NP specimen assays to show that the expression levels of TLR9, NF-κB, and NLRP3 inflammasomes correlated with the degree of IVDD. We demonstrated that mtDNA mediated TLR9-NF-κB-NLRP3 axis activation in oxidative stress-induced human NPC pyroptosis in vitro. Oxidative stress can damage the mitochondria of NPCs, causing the opening of the mitochondrial permeability transition pores (mPTP) and leading to the release of mtDNA into the cytosol. Furthermore, inhibition of mPTP opening or TLR9 activation blocked TLR9-NF-κB-NLRP3 axis activation and thereby mediated NPC pyroptosis and IVDD.
conclusionmtDNA plays a key role in mediating NPC pyroptosis and IVDD via the TLR9-NF-κB-NLRP3 axis. Our findings provide new potential targets for IVDD.
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