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Updated: Aug 19, 2026
Induction of Periodontitis via a Combination of Ligature and Lipopolysaccharide Injection in a Rat Model
Published on: February 17, 2023
Proteinase-activated receptor-2 (PAR2) agonist causes periodontitis in rats
M Holzhausen1, L C Spolidorio, N Vergnolle
1Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, 3330 Hospital Drive, NW, Calgary, T2N 4N1, Alberta, Canada.
Abstract:
Proteinase-activated receptor-2 (PAR2) is a G-protein-coupled receptor that mediates cellular responses to extracellular proteinases. Since PAR2 is expressed by oral epithelial cells, osteoblasts, and gingival fibroblasts, where its activation releases interleukin-8, we hypothesized that PAR2 activation may participate in periodontal disease in vivo. We investigated the role of PAR2 activation in periodontal disease in rats. Radiographic and enzymatic (myeloperoxidase) analysis revealed that topical application of PAR2 agonist causes periodontitis but also exacerbates existing periodontitis, leading to significant alveolar bone loss and gingival granulocyte infiltration. Inhibition of matrix metalloproteinase (MMP) and cyclo-oxygenase (COX) decreased PAR2 agonist-induced periodontitis. More specifically, the overexpression of COX-1, COX-2, MMP-2, and MMP-9 in gingival tissues suggests that they are involved in PAR2-induced periodontitis. In conclusion, PAR2 agonist causes periodontitis in rats through a mechanism involving prostaglandin release and MMP activation. Inhibition of PAR2 may represent a novel approach to modulate host response in periodontitis.
Insights
Activation of Proteinase-activated receptor-2 (PAR2) causes periodontitis in rats by increasing interleukin-8 release. Inhibiting PAR2 may offer a new strategy for treating periodontal disease.
Area of Science:
- Oral biology
- Immunology
- Pharmacology
Background:
- Proteinase-activated receptor-2 (PAR2) is a G-protein-coupled receptor involved in cellular responses to proteinases.
- PAR2 is present in oral epithelial cells, osteoblasts, and gingival fibroblasts, mediating interleukin-8 release.
- The role of PAR2 in periodontal disease pathogenesis in vivo remains largely unexplored.
Purpose of the Study:
- To investigate the role of PAR2 activation in the development and exacerbation of periodontal disease in a rat model.
- To elucidate the mechanisms underlying PAR2-induced periodontitis, focusing on matrix metalloproteinase (MMP) and cyclo-oxygenase (COX) pathways.
Main Methods:
- Periodontitis was induced in rats via topical application of a PAR2 agonist.
- Radiographic analysis was used to assess alveolar bone loss.
- Enzymatic analysis (myeloperoxidase) and gene expression analysis (COX-1, COX-2, MMP-2, MMP-9) were performed on gingival tissues.
- The effects of MMP and COX inhibition on PAR2 agonist-induced periodontitis were evaluated.
Main Results:
- Topical application of PAR2 agonist induced periodontitis, characterized by significant alveolar bone loss and gingival granulocyte infiltration.
- PAR2 activation exacerbated existing periodontitis.
- Inhibition of MMP and COX pathways significantly reduced PAR2 agonist-induced periodontitis.
- Overexpression of COX-1, COX-2, MMP-2, and MMP-9 was observed in gingival tissues, indicating their involvement.
Conclusions:
- PAR2 activation triggers periodontitis in rats through a mechanism involving prostaglandin release and MMP activation.
- PAR2 plays a significant role in the pathogenesis of periodontal disease.
- Inhibition of PAR2 presents a potential novel therapeutic strategy for modulating host responses in periodontitis.
