ArticleCell communication and signaling : CCS2021
Mitochondrial DNA leakage induces odontoblast inflammation via the cGAS-STING pathway.
Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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76 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- Impact of tumor immunotherapy on kidney injury and multi-organ outcomes: a mechanistic and clinical perspective.Frontiers in immunology · 2026Pooled it
- Pioneering next-generation bioactive materials for endodontics: Insights of mitochondrial biology.Bioactive materials · 2026Article
- A Novel piRNA-Mediated Epigenetic Axis: piR-36241 Exacerbates Pulpitis by Silencing the Protective Receptor ADGRG2 in Human Dental Pulp Stem Cells.International endodontic journal · 2026Article
- Spatial Transcriptomics Delineates the Inflammatory Landscape of Human Dental Pulp: Regional Crosstalk and Therapeutic Implications.International endodontic journal · 2026Article
- Leptin attenuates heat stress-induced mitoxyperilysis in porcine Sertoli cells by suppressing the mtDNA-cGAS-STING axis.Journal of animal science and biotechnology · 2026Article
- Mitochondrial DNA leakage in oocytes activates cGAS-STING signaling to drive ovarian aging.Nature aging · 2026Article
- Closed-loop iron chelate recycling via molecularly imprinted hydrogels suppresses ferroptosis.Nature communications · 2026Article
- The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.Biomarker research · 2026Review
- Extracellular vesicles derived from stem cells of human exfoliated deciduous teeth alleviate pulpitis through attenuation of mitochondrial dysfunction.Stem cell research & therapy · 2026Article
- Anti-Inflammatory Properties ofPlants (Basel, Switzerland) · 2026Article
- Targeting VDAC1 to protect against mitochondria-linked cell death pathways: apoptosis, pyroptosis, ferroptosis, and associated diseases.Apoptosis : an international journal on programmed cell death · 2026Article
- Mitochondrial DNA as a driver of inflammation via the cGAS-STING pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- AQP4-IgG-Induced Astrocyte-Derived Small Extracellular Vesicles Carrying Mitochondrial DNA Regulate the TLR9/MyD88/NF-κB Pathway to Drive Microglial Activation and Neuromyelitis Optica.Neurochemical research · 2026Article
- Vagus Nerve Stimulation Attenuates Cognitive Impairment in Traumatic Brain Injury via the mtDNA/cGAS-STING/NLRP3 Inflammasome Axis.Neurocritical care · 2026Article
- Ferroptosis inhibits cementoblast mineralization via cGAS-STING/GPX4 axis.Progress in orthodontics · 2026Article
- Exercise-modulated IL-6 in cancer cachexia: molecular mechanisms and therapeutic potential.Journal of translational medicine · 2026Review
- Icariside II protects against neuronal injury by modulating PI3K/AKT-dependent mitochondrial dynamics and apoptosis in Alzheimer's disease models.Frontiers in pharmacology · 2026Article
- Delaying cardiac aging: potential mechanisms centered on PANoptosis and targeted intervention strategies.Frontiers in cardiovascular medicine · 2026Review
- Intercellular mitochondrial transfer in melanoma progression and therapeutic resistance: mechanisms and targeting potential.Frontiers in oncology · 2026Review
- Pathogenic role of mitochondrial DNA mutations in heart failure: clinical features, mechanisms, and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
16 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway activation in infectious diseases. Odontoblasts are the first cells challenged by cariogenic bacteria and involved in maintenance of the pulp immune and inflammatory responses to dentine-invading pathogens. In this study, we investigated that mtDNA as an important inflammatory driver participated in defending against bacterial invasion via cGAS-STING pathway in odontoblasts.
methodsThe normal tissues, caries tissues and pulpitis tissues were measured by western blotting and immunohistochemical staining. Pulpitis model was built in vitro to evaluated the effect of the cGAS-STING pathway in odontoblast-like cell line (mDPC6T) under inflammation. Western blot and real-time PCR were performed to detect the expression of cGAS-STING pathway and pro-inflammatory cytokines. The mitochondrial function was evaluated reactive oxygen species (ROS) generated by mitochondria using MitoSOX Red dye staining. Cytosolic DNA was assessed by immunofluorescent staining and real-time PCR in mDPC6T cells after LPS stimulation. Furthermore, mDPC6T cells were treated with ethidium bromide (EtBr) to deplete mtDNA or transfected with isolated mtDNA. The expression of cGAS-STING pathway and pro-inflammatory cytokines were measured.
resultsThe high expression of cGAS and STING in caries and pulpitis tissues in patients, which was associated with inflammatory progression. The cGAS-STING pathway was activated in inflamed mDPC6T. STING knockdown inhibited the nuclear import of p65 and IRF3 and restricted the secretion of the inflammatory cytokines CXCL10 and IL-6 induced by LPS. LPS caused mitochondrial damage in mDPC6T, which promoted mtDNA leakage into the cytosol. Depletion of mtDNA inhibited the cGAS-STING pathway and nuclear translocation of p65 and IRF3. Moreover, repletion of mtDNA rescued the inflammatory response, which was inhibited by STING knockdown.
conclusionOur study systematically identified a novel mechanism of LPS-induced odontoblast inflammation, which involved mtDNA leakage from damaged mitochondria into the cytosol stimulating the cGAS-STING pathway and the inflammatory cytokines IL-6 and CXCL10 secretion. The mtDNA-cGAS-STING axis could be a potent therapeutic target to prevent severe bacterial inflammation in pulpitis. Video Abstract.
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