Fibrin aggravates periodontitis through inducing NETs formation from mitochondrial DNA

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.