Hepatocyte growth factor exerts promoting functions on murine dental papilla cells

Hepatocyte growth factor (HGF) is a potent mitogenic and angiogenic factor involved in the development of many tissues including the teeth. We previously reported that dental pulp cells express the HGF receptor c-met and that HGF can enhance cell proliferation and differentiation. The purpose of this study was to determine whether HGF could stimulate proliferation and/or differentiation of murine dental papilla cells (MDPCs). MDPCs were isolated from neonatal mice, and the mitogenic potential of HGF on MDPCs was measured by 3-(4, 5-dimethyl-thyazol-2-yl)-2, 5-diphenyltetrazolium and flow cytometry. Differentiation of MDPCs in the presence of HGF was characterized by mineralization assay, alkaline phosphatase (ALP) activity and reverse-transcription polymerase chain reaction. We reported that MDPCs expressed both HGF and c-met and that HGF enhanced proliferation of MDPCs by concentrations ranging from 5 ng/mL to 20 ng/mL, with 10 ng/mL as the optimal concentration (p < 0.05). HGF prolonged S phase and shortened G1 phase of MDPCs, increased ALP activity significantly over the control (p < 0.05), and enhanced the formation of mineral nodules. ALP, dentin sialophosphoprotein, and dentin matrix protein-1 expression were significantly increased in the presence of HGF (p < 0.05), as were the expression of Msx1, Runx2, and Pax9. Our data suggest that HGF plays an important role in tooth development, by promoting the proliferation and differentiation of MDPCs.