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Proteinase-activated Receptor-2 (PAR₂) Agonist Causes Periodontitis in Rats

¹ Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, 3330 Hospital Drive, NW, Calgary, T2N 4N1, Alberta, Canada; and
² Department of Oral Pathology, Dental School of Araraquara, State University of São Paulo (UNESP), Araraquara, São Paulo, Brazil;

Correspondence: ^* corresponding author, nvergnol{at}ucalgary.ca

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.

Key Words: proteinase-activated receptor-2 • alveolar bone loss • inflammation • matrix metalloproteinase • cyclo-oxygenase • periodontitis

Journal of Dental Research, Vol. 84, No. 2, 154-159 (2005)
DOI: 10.1177/154405910508400209


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