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Updated: Jun 3, 2025

Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
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Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils

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Dynamin-Related Protein 1 Orchestrates Inflammatory Responses in Periodontal Macrophages via Interaction

Yiming Jiang1, Zihan Wang2, Kaige Zhang2

  • 1The VIP Department, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China.

Journal of Clinical Periodontology
|January 6, 2025
PubMed
Abstract

Insights

Dynamin-related protein 1 (Drp1) hyperactivation in macrophages drives inflammation in periodontitis by promoting mitochondrial dysfunction and NLRP3 inflammasome activation through interaction with hexokinase 1 (HK1).

Area of Science:

  • Immunology
  • Cell Biology
  • Mitochondrial Biology

Background:

  • Periodontal disease involves chronic inflammation driven by macrophages.
  • Mitochondrial dysfunction is increasingly recognized as a key factor in inflammatory diseases.
  • The role of dynamin-related protein 1 (Drp1) in macrophage-mediated periodontal inflammation requires elucidation.

Purpose of the Study:

  • To investigate the role of mitochondrial dysfunction in initiating periodontal inflammation.
  • To determine how Drp1 contributes to macrophage inflammatory responses via interaction with hexokinase 1 (HK1).

Main Methods:

  • Analysis of gingival tissues from periodontitis patients and healthy controls.
  • Stimulation of THP-1 and RAW264.7 macrophages with Porphyromonas gingivalis (Pg) components.
  • Assessment of Drp1 activation, mitochondrial dynamics, and inflammatory markers (NLRP3, caspase-1, IL-1β, GSDMD) using Western blot and immunofluorescence.
  • Verification of Drp1-HK1 interaction via immunoprecipitation.

Main Results:

  • Overactivated Drp1 was observed in periodontitis tissues and stimulated macrophages, correlating with NLRP3 inflammasome activation and inflammatory factor release.
  • A direct interaction between Drp1 and HK1 was identified, leading to excessive mitochondrial permeability transition pore (mPTP) opening and mitochondrial dysfunction.
  • Drp1 hyperactivation promoted inflammatory responses in periodontal macrophages.

Conclusions:

  • Drp1 hyperactivation in macrophages contributes to inflammation induction within the periodontal tissue microenvironment.
  • Drp1 modulates inflammatory responses in periodontal macrophages, notably by facilitating mPTP opening and subsequent mitochondrial dysfunction.
Keywords:
dynamin‐related protein 1hexokinase 1inflammasomemitochondrial permeability transition poreperiodontitis

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