The Role of Proteinase-Activated Receptors 1 and 2 in the Regulation of Periodontal Tissue Metabolism and Disease

Proteinase-activated receptors 1 (PAR(1)) and 2 (PAR(2)) are the most highly expressed members of the PAR family in the periodontium. These receptors regulate periodontal inflammatory and repair processes through their activation by endogenous and bacterial enzymes. PAR(1) is expressed by the periodontal cells such as human gingival fibroblasts, gingival epithelial cells, periodontal ligament cells, osteoblasts, and monocytic cells and can be activated by thrombin, matrix metalloproteinase 1 (MMP-1), MMP-13, fibrin, and gingipains from Porphyromonas gingivalis. PAR(2) is expressed by neutrophils, osteoblasts, oral epithelial cells, and human gingival fibroblasts, and its possible activators in the periodontium are gingipains, neutrophil proteinase 3, and mast cell tryptase. The mechanisms through which PARs can respond to periodontal enzymes and result in appropriate immune responses have until recently been poorly understood. This review discusses recent findings that are beginning to identify a cardinal role for PAR(1) and PAR(2) on periodontal tissue metabolism.