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Author Spotlight: Enhancing Dental Pulp Research with Improved Mouse Models
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Multiple cell death modalities and immune response in pulpitis.

Ben Wang1,2,3, Wenwen Li1,2,3, Weiying Huang1,2,3

  • 1Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, P.R. China.

International Endodontic Journal
|September 11, 2024
PubMed
Summary

Pulpitis involves distinct cell death patterns, with neutrophil extracellular traps (NETosis) specifically in abscess areas. Pulpitis also increases bone marrow neutrophil activity, suggesting potential diagnostic strategies targeting NETs.

Keywords:
NETosisneutrophilspulpitispulpitis with necrosispulpitis without necrosisregulated cell death

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Area of Science:

  • Oral Biology
  • Immunology
  • Cellular Pathology

Background:

  • Pulpitis, an inflammatory condition of the dental pulp, can progress to necrosis, significantly impacting tooth vitality.
  • Regulated cell death (RCD) pathways, including apoptosis, pyroptosis, necroptosis, and NETosis, are implicated in inflammatory processes but their distinct roles in pulpitis are not fully elucidated.

Purpose of the Study:

  • To investigate the differential expression and distribution of apoptosis, pyroptosis, necroptosis, and NETosis in human pulpitis with and without necrosis.
  • To evaluate the systemic effects of pulpitis with necrosis (PWN) on peripheral and bone marrow (BM) neutrophils, and spleen lymphocytes in a mouse model.

Main Methods:

  • Histological classification of human dental pulp into healthy pulp (HP), pulpitis without necrosis (PWON), and pulpitis with necrosis (PWN).
  • Immunohistochemical and immunofluorescent staining for RCD markers (caspase-8, cleaved caspase-3, caspase-1, gasdermin D, RIPK3, MLKL, MPO, citrullinated histone H3).
  • Induction of pulpitis in mice, followed by flow cytometry analysis of neutrophils and lymphocytes, and in vitro studies on human dental pulp stem cells (hDPSCs).

Main Results:

  • PWN exhibited significantly higher levels of total necrotic cells, apoptosis, pyroptosis, and notably NETosis, particularly in the abscess core.
  • Myeloperoxidase (MPO), a marker for NETosis, was predominantly found in the abscess core of PWN.
  • Pulpitis induction in mice increased the number and activity of bone marrow neutrophils, while peripheral blood and spleen lymphocyte populations remained unchanged.

Conclusions:

  • Distinct patterns of mixed regulated cell death occur at different histological stages of pulpitis.
  • NETosis is a specific and predominant feature in the abscess area of pulpitis, suggesting its role in disease progression.
  • The observed changes in bone marrow neutrophils highlight systemic immune responses to pulpitis, and NETosis may offer a target for diagnostic strategies in vital pulp therapy.