The Role of BDNF/TrkB in TNFα-Induced Odontoblastic DPSC Differentiation

Objectives: Dental caries is the most common tooth disease worldwide that is caused by multiplex interaction of bacteria. Reparative dentinogenesis is accompanied by intense inflammation that initiates stem/progenitor cell recruitment by odontoblast-like cells. The majority of the attention has been given to direct dentinogenesis, while few studies have explored the role of inflammation in this process. Brain derived neurotrophic factor (BDNF) is a nerve growth factor-related gene family molecule which functions through tropomyosin receptor kinase B (TrkB). While the roles of BDNF in neural repair and other regeneration processes are well-identified, its role in dentinogenesis has not been explored. Furthermore, the role of BDNF receptor-TrkB in inflammation-induced dentinogenesis remains unknown. The aim of this study is to determine the role of BDNF/TrkB in TNFα -induced dental pulp stem cells (DPSC) odontoblastic differentiation.
Methods: The role of BDNF/TrkB was examined during 17-day odontogenic DPSC differentiation. Human DPSCs were subjected to odontogenic differentiation in osteogenic media treated with TNFα, BDNF and TrkB agonist.
Results: Immunofluorescent data confirmed the expression of BDNF and TrkB on day 4 differentiation. Our ELISA and qPCR data demonstrated that TrkB agonist (LM22A-4) treatment increased the dentin matrix protein-1 (DMP-1) expression during early DPSC odontoblastic differentiation. Coherently, the expression of runt related transcription factor 2 and osteocalcin are increased. Odontoblastic differentiation of DPSCs associated with caries injury undergoes in an inflammatory context. TNFα, which is responsible for a diverse range of inflammation signaling, increased the dentin sialophosphoprotein (DSPP) and DMP1 expression. Furthermore, BDNF significantly potentiated its effect. Application of both TNFα and TrkB antagonist (CTX-B) showed a decreased expression of DSPP and DMP1 compared to TNFα and BDNF treatment.
Conclusions: These data suggest that BDNF and TrkB activation increase TNFα-stimulated DPSC odontoblastic differentiation. Our study addresses a novel regulatory pathway and a therapeutic approach in DPSC engineering in dentinogenesis.