Effect of protease activated receptor 1 (PAR1) activation on osteogenic activity of periodontal ligament cells

Abstract

Protease activated receptor 1 (PAR1) activation by thrombin can play an important role on periodontal tissue homeostase and healing. A recent study from our group has shown an increased expression of PAR1 in gingival crevicular fluid cells of chronic periodontitis patients after periodontal treatment, and that PAR1 expression is associated with decreased levels of inflammatory biomarkers. In addition, previous in vitro studies showed that PAR1 activation by thrombin leads to: osteoprotegerin (OPG) production in periodontal ligament cells, a dose-response increase in the proliferation of isolated bone marrow stromal cells of rats, and leads to an increased expression of several growth factors in osteoblasts. Therefore, these studies suggest an important mediator role of PAR1 on periodontal tissue repair. In the present study, we hypothesized that PAR1 activation in periodontal ligament cells can lead to an increased osteogenic activity. Therefore, the main objective of the present study is to evaluate the effect of PAR1 activation by thrombin on the osteogenic differentiation of ligament cells. In addition, the effects of PAR1 activation on mineralized matrix production and on the genetic and proteic expression of alkaline phosphatase, osteopontin, osteocalcin, RANKL, OPG, runt-related transcription factor-2 (Runx2), IL-10 and TGF-ß1 will also be evaluated. (AU)