Fibrin aggravates periodontitis through inducing NETs formation from mitochondrial DNA
Related Experiment Video
Updated: Jun 19, 2025

Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
Yinan Chen1,2,3, Enhua Mei1,2,3, Shunxue Nan1,2,3
1Department of Preventive Dentistry, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.
Objectives:
This study investigated the role of fibrin on neutrophil extracellular traps (NETs) formation from neutrophils and to elucidate the involvement of mitochondria in NETs formation during periodontitis.
Materials And Methods:
Plasminogen-deficient (Plg-/-) mice were employed to evaluate the effects of fibrin deposition on inflammation, bone resorption, and neutrophil infiltration in periodontal tissues. In addition, in vitro tests evaluated fibrin's impact on neutrophil-driven inflammation. Mitochondrial reactive oxygen species (mtROS) levels within neutrophils were quantified utilizing flow cytometry and immunofluorescence in vitro. Furthermore, the anti-inflammatory properties of the mtROS scavenger, Mito-TEMPO, were confirmed to regulate the NET formation in vitro and in vivo.
Results:
Plasminogen deficiency resulted in increased fibrin deposition, neutrophil infiltration, inflammatory factors concentration, and alveolar bone resorption in periodontal tissues. After neutrophils were treated by fibrin in vitro, the expression of inflammatory factors, the formation of mtROS, and NETs enriched in mitochondrial DNA (mtDNA) were upregulated, which were reversed by Mito-TEMPO in vitro. Moreover, Mito-TEMPO alleviated inflammation in Plg-/- mice.
Conclusions:
This study showed that fibrin deposition in gingiva induced the NET formation in Plg-/- mice, in which the DNA in NETs was from mitochondria depending on increasing mtROS.
Insights
Fibrin deposition in periodontitis promotes neutrophil extracellular trap (NET) formation. Mitochondria-derived reactive oxygen species (mtROS) drive this process, with a scavenger mitigating NETs and inflammation.
Area of Science:
- Periodontology
- Immunology
- Cell Biology
Background:
- Periodontitis involves inflammation and bone loss.
- Neutrophil extracellular traps (NETs) contribute to inflammatory diseases.
- Mitochondria play a role in cellular inflammation.
Purpose of the Study:
- Investigate fibrin's role in NET formation during periodontitis.
- Elucidate the involvement of mitochondria in NET formation.
- Assess the therapeutic potential of targeting mitochondrial pathways.
Main Methods:
- Utilized plasminogen-deficient (Plg-/-) mice to study fibrin deposition effects.
- Conducted in vitro experiments on neutrophils exposed to fibrin.
- Quantified mitochondrial reactive oxygen species (mtROS) using flow cytometry and immunofluorescence.
- Evaluated the efficacy of mtROS scavenger Mito-TEMPO in vitro and in vivo.
Main Results:
- Plg deficiency led to increased fibrin, neutrophil infiltration, inflammation, and bone resorption.
- In vitro, fibrin induced inflammatory factors, mtROS, and NET formation (mtDNA-enriched).
- Mito-TEMPO reversed these effects in vitro and reduced inflammation in Plg-/- mice.
Conclusions:
- Fibrin deposition in gingiva induces NET formation in periodontitis.
- Mitochondrial-derived mtROS are crucial mediators of fibrin-induced NET formation.
- Targeting mtROS with Mito-TEMPO offers a potential therapeutic strategy for periodontitis.
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Published on: November 1, 2019
06:14Induction of Periodontitis via a Combination of Ligature and Lipopolysaccharide Injection in a Rat Model
Published on: February 17, 2023
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