Proteinase-activated receptor-2 (PAR2) agonist causes periodontitis in rats

Proteinase-activated receptor-2 (PAR(2)) is a G-protein-coupled receptor that mediates cellular responses to extracellular proteinases. Since PA R-2 is expressed by oral epithelial cells, osteoblasts, and gingival fibroblasts, where its activation releases interleukin-8, we hypothesized that PAR(2) activation may participate in periodontal disease in vivo. We investigated the role of PAR(2) activation in periodontal disease in rats. Radiographic and enzymatic (myeloperoxidase) analysis revealed that topical application of PAR(2) 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 PAR(2) 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 PAR(2)-induced periodontitis. In conclusion, PAR(2) agonist causes periodontitis in rats through a mechanism involving prostaglandin release and MMP activation. Inhibition of PAR(2) may represent a novel approach to modulate host response in periodontitis.