The role of FAPalpha in dental stem cells and root development

Abstract

Fibroblast activation protein-alpha (FAP') is a membrane protein with type I collagenase activity expressed during embryogenesis. Reaching adolescence, FAP' expression decreases, only increasing during wound healing, tumour growth or myocardial infarction. FAP' expression was recently observed in bone-marrow mesenchymal stem cells (MSCs) and ongoing research from our group revealed its presence on MSCs from the dental tissue. In this project, we hypothesized that FAP' plays an important role in dental root development. For that we aimed to study FAP' expression in dental stem cells involved in root development; dental follicle stem cells (DFSCs) and Hertwig's Epithelial Root Sheath (HERS), a bilayer of epithelial cells, and Stem Cells from the Apical Papilla (SCAPs), providing information about this tissue. The expression of FAP' was also studied in ameloblastoma, a tumour provoked during tooth development. To achieve this, a characterization through immunohistochemistry and immunofluorescence analysis was performed. We report the presence of FAP' on DFSCs and SCAPs. We also provided insights in the apical papilla identifying two regions: cortex fibrosa, at the periphery, and medulla, in the core, both positive for FAP'. TGF-'1 and SDF-1 were found in the cortex fibrosa co-located with FAP' and SCAPs showed enhanced migration in response to SDF-1. FAP' was also identified in ameloblastoma. These results suggest a role of FAP' in the migration of dental stem cells during root maturation related to its collagenase function.