The multipotent nature of dental pulp stem cells (DPSCs) promises regenerative endodontic potentials.
Alterations in microenvironment have been shown to control the differentiation phenotypes of DPSCs.
Understanding the biological mechanisms and finding the optimal DPSC differentiation protocols are
crucial for successful DPSC engineering strategies in pulp and dentin healing. The aim of this study is to
identify the role of p38 mitogen-activated protein kinase (p38) under normal and oxygen-deprived
conditions (2%) to reveal its effect on odontogenic DPSC differentiation. Human DPSCs were isolated from
healthy molars and underwent odontogenic differentiation in regular and osteogenic media treated with
SB203580, a p38 inhibitor, for 72 hours, and then swapped with osteogenic media for 21 days under hypoxic
condition. Immunochemistry and PCR analysis for the various odontogenic differentiation genes and
proteins were performed. Our PCR data demonstrate that p38 inhibition resulted in a significant
upregulation in odontogenic gene expressions such as DMP-1, DSPP, RUNX, and OSX in normal
conditions. Under hypoxia, this effect was reversed. These results were further supported by DSPP
immunohistochemistry. The DSPP expression under hypoxia was significantly weaker compared to the
control. Our results indicate that p38 represents a negative regulator of the odontogenic DPSC
differentiation in normoxia. Under hypoxia, p38 exerts a positive function of DPSC differentiation. Taken
together, we identified the p38 and oxygen level as crucial factors to control odontogenic DPSC
differentiation providing their essential roles in designing for successful pulp-dentin complex engineering
strategies.
p38 MAP Kinase-Mediated Odontogenic Differentiation of Dental Pulp Stem Cells
