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Updated: May 31, 2026
Induction of Periodontitis via a Combination of Ligature and Lipopolysaccharide Injection in a Rat Model
Published on: February 17, 2023
Oral treatment with complement factor C5a receptor (CD88) antagonists inhibits experimental periodontitis in rats
T Breivik1, Y Gundersen, P Gjermo
1Department of Periodontology, Faculty of Dentistry, University of Oslo, Oslo, Norway. tbreivik@odont.uio.no
Background And Objective:
The complement activation product 5a (C5a) is a potent mediator of the innate immune response to infection, and may thus also importantly determine the development of periodontitis. The present study was designed to explore the effect of several novel, potent and orally active C5a receptor (CD88) antagonists (C5aRAs) on the development of ligature-induced periodontitis in an animal model.
Material And Methods:
Three different cyclic peptide C5aRAs, termed PMX205, PMX218 and PMX273, were investigated. Four groups of Wistar rats (n = 10 in each group) were used. Starting 3 d before induction of experimental periodontitis, rats either received one of the C5aRas (1-2 mg/kg) in the drinking water or received drinking water only. Periodontitis was assessed when the ligatures had been in place for 14 d.
Results:
Compared with control rats, PMX205- and PMX218-treated rats had significantly reduced periodontal bone loss.
Conclusion:
The findings suggest that complement activation, and particularly C5a generation, may play a significant role in the development and progression of periodontitis. Blockade of the major C5a receptor, CD88, with specific inhibitors such as PMX205, may offer novel treatment options for periodontitis.
Insights
Novel C5a receptor antagonists reduced bone loss in experimental periodontitis. Blocking complement activation via CD88 may offer new treatments for this inflammatory gum disease.
Area of Science:
- Immunology
- Periodontology
- Pharmacology
Background:
- Complement activation product 5a (C5a) is a key mediator in innate immunity and infection.
- C5a may significantly influence the development and progression of periodontitis.
- The C5a receptor (CD88) is a potential therapeutic target for periodontitis.
Purpose of the Study:
- To investigate the efficacy of novel, orally active C5a receptor antagonists (C5aRAs) in a ligature-induced periodontitis model.
- To explore the role of C5a signaling in periodontitis pathogenesis.
Main Methods:
- Three cyclic peptide C5aRAs (PMX205, PMX218, PMX273) were administered to Wistar rats.
- Rats received C5aRAs in drinking water starting 3 days before ligature placement.
- Periodontitis was assessed after 14 days of ligature placement.
Main Results:
- Treatment with PMX205 and PMX218 significantly reduced periodontal bone loss compared to controls.
- PMX273 did not show a significant effect on bone loss in this model.
- These findings indicate a protective effect of specific C5aRAs against periodontitis progression.
Conclusions:
- Complement activation, specifically C5a generation, appears to play a crucial role in periodontitis.
- Blockade of the C5a receptor (CD88) using inhibitors like PMX205 presents a promising therapeutic strategy.
- Targeting C5a signaling offers potential novel treatment options for periodontitis.
