Osteogenic effect of activation of PAR1 receptor in cell sheets synthetized by stem cell from periodontal ligament cells

• Grant number: 18/15740-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2018
• Effective date (End): September 30, 2019
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Marinella Holzhausen Caldeira
• Grantee: Danilo Andrés Balzarini
• Host Institution: Faculdade de Odontologia (FO). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Periodontal disease is highly prevalent and has as a characteristic the reabsorption of the periodontal ligament, cementum and alveolar bone. The regeneration of damaged tissues and organs is considered the ideal outcome of a treatment and has been sought through biological solutions once that traditional methods used for the treatment of bone defects have presented limitations. In this way, recent efforts in the treatment of periodontal disease have focused on regenerative approaches based on cells. Cell-sheets have attracted extensive attention to repair/regenerate periodontal defects by being able to allow osteoblastic proliferation and to support the formation of mineralized matrix. Obtaining cell sheets, by detaching the cell layer from the culture plate (without dissociation of the cells) is a method that has stood out in the current scenario. Additionally, periodontal ligament stem cells (PDLSCs) are able to differentiate into cementoblasts/osteoblasts, adipocytes and collagen-forming cells, contributing to periodontal tissue regeneration. It is known that the type 1 protease-activated receptor (PAR 1) plays a crucial role in initiating and maintaining inflammation and repairing fractures, regulating various aspects of osteoblast function. Recently, our research group has observed that the activation of PAR 1 is able to increase the osteogenic activity of PDLSCs. However, the mechanism by which this process is performed has not yet been fully elucidated and its role through the use of cell membranes has not yet been studied. Thus, the main objective of this work will be to evaluate the effect of PAR 1 activation on in vitro osteogenic activity in cell membranes obtained from PDLSCs activated with the activating peptide of PAR 1 in order to develop a new therapeutic approach that may in the treatment of periodontal defects. In addition, the present work will evaluate the possible signaling pathways and transcription factors involved in the process of osteogenesis mediated by PAR 1 in PDLSCs.