Evidence map›Paper›PMID 34016129›Full record

ArticleCell communication and signaling : CCS2021

Mitochondrial DNA leakage induces odontoblast inflammation via the cGAS-STING pathway.

Lu Zhou, Yi-Fei Zhang, Fu-Hua Yang, Han-Qing Mao, Zhi Chen, Lu Zhang

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 1 pooled it
6.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

  1. Pooled it
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  10. Anti-Inflammatory Properties ofPlants (Basel, Switzerland) · 2026
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  12. Mitochondrial DNA as a driver of inflammation via the cGAS-STING pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Lu ZhouThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Yi-Fei ZhangThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Fu-Hua YangThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Han-Qing MaoThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Zhi ChenThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Lu ZhangThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China. luzhang2012@whu.edu.cn.ORCID 0000-0001-9049-8807
Wuhan University · CN

Funding

National Natural Science Foundation of China 81771064National Natural Science Foundation of China 81974148
6 · The paper itself

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.

Indexed as

Signal TransductionCell LineCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseCytosolDental CariesDNA, MitochondrialHumansInflammationLipopolysaccharidesMembrane ProteinsMitochondriaNucleotidyltransferasesOdontoblastsPulpitisSTING ProteincGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA, MitochondrialLipopolysaccharidesMembrane ProteinsNucleotidyltransferasesSTING1 protein, humanSTING ProteincGAS-STING pathwayImmune responseInflammationMitochondrial damageMitochondrial DNAOdontoblasts

Identifiers

PMID34016129
PMCPMC8136190
OpenAlexW3161508117

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Registered trials

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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.