Key result
Topical PAR2 agonist causes and exacerbates periodontitis in rats, driving significant alveolar bone loss.
Why the study?
PAR2 is expressed in oral cells and may participate in periodontal disease, but its role in vivo was not established.
PAR2 agonists warrant caution in periodontal contexts; this rat study leaves open therapeutic targeting of PAR2 in human periodontitis.
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.
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Holzhausen et al. (2005) studied Periodontal disease. PAR2 agonist was evaluated on Periodontitis (alveolar bone loss and gingival granulocyte infiltration). Topical application of PAR2 agonist caused and exacerbated periodontitis in rats, leading to significant alveolar bone loss and gingival granulocyte infiltration.
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