Insights from in vitro and in vivo studies evaluating the Protease Activated Receptor 1 (PAR1) potential pathways and associated osteogenic outcomes

Periodontal disease has a high prevalence in the worldwide population and can evolve to a destruction process of periodontal support structures: cementum, alveolar bone and periodontal ligament. Regeneration of damaged tissues and organs is considered to be the ultimate treatment objective and has been sought through biological solutions since the current surgical regenerative treatments present some limitations. Thus, recent efforts in the treatment of periodontal disease have focused on cell-based regenerative approaches and cell sheets derived from human periodontal ligament stem cells (hPDLSCs) have attracted wide attention for its regeneration potential as they are able to allow osteoblastic proliferation and to support mineralized matrix formation. The protease-activated receptor type 1 (PAR1) is a widely known G-protein coupled receptor that plays a crucial role in the initiation and maintenance of inflammation and fracture repair, regulating various aspects of osteogenesis and our group has observed that the activation of PAR1 is able to increase the osteogenic activity in hPDLSCs. However, whether PAR1 shows the same effect on hPDLSCs cell sheets is still unknown. The purpose of this study was to evaluate the effect of PAR1 activation on the osteogenic activity in cellsheets obtained from hPDLSCs in an in vivo ectopic bone formation model and to evaluate the cementogenic gene expression outcome related to PAR1 activation under the blockade of PI3K and MAPK/ERK intracellular pathways in hPDLSCs. (AU)