Proteinase-activated receptor-2 (PAR2) agonist causes periodontitis in rats.
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.
Holzhausen
M
M
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, 3330 Hospital Drive, NW, Calgary, T2N 4N1, Alberta, Canada.
Spolidorio
L C
LC
Vergnolle
N
N
D016301:Alveolar Bone Loss / Q000276:immunology / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005881:Gingiva / Q000276:immunology / Q000378:metabolism*; D006098:Granulocytes / Q000276:immunology; D008297:Male; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000276:immunology; D009842:Oligopeptides; D010518:Periodontitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000276:immunology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000819:agonists* / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009842:Oligopeptides; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D011451:Prostaglandin-Endoperoxide Synthases; D020782:Matrix Metalloproteinases