The Effect of Simvastatin on Odontoblastic Differentiation of Human Dental Pulp Stem Cells: An In Vitro Study

<b>Objectives:</b> The aim of the current in vitro study was to assess the effect of simvastatin on the early-stage differentiation of human dental pulp stem cells (hDPSCs) in an odontogenic pattern by evaluating the expression of specific odontogenic-related genes. <b>Methods:</b> hDPSCs were cultured in the presence of different concentrations of simvastatin (0.1, 0.5, 1, 5, and 10 µM) to evaluate cytotoxicity. Moreover, osteogenic differentiation was assessed by Alkaline Phosphatase (ALP) activity and alizarin red staining (ARS) after 7 days of culture. Finally, odontogenic-related gene (OCN, MEPE, DSPP, and DMP-1) expression analysis was performed. <b>Results:</b> Three days after treatment, higher concentrations of simvastatin (1, 5, and 10 µM) significantly limited cell viability. Upregulation of ALP activity and odontoblastic cell-related genes (OCN and MEPE) was observed in the presence of 1 µM simvastatin. The expression was statistically higher for ALP (<i>p</i> = 0.0001) and OCN (<i>p</i> = 0.0231). On the other hand, comparable or slightly less effect concerning mineralization ability with respect to the control group, as well as in the expression of DSPP and DMP-1, was observed. <b>Conclusions:</b> Simvastatin demonstrated a positive influence on dentinogenesis by improving the expression of specific markers such as MEPE and OCN. However, its effect on inflammation reduction and the potential to be used in combination with other materials should be further assessed. Simvastatin might be successfully applied in the regeneration of damaged dental pulp tissues and promotion of reparative dentinogenesis. Additional studies should be carried out to support the obtained outcomes.