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Hepatocyte growth factor (HGF) is mesenchymal-derived growth factor acting through a transmembrane tyrosine kinase receptor, c-met. HGF has multiple effects on different cells. However, its function in dentinogenesis remains unclear. In this study, the expression of HGF in human dental pulp cells (DPCs) in vitro was studied by immunostaining and RT-PCR. The effect of HGF on DPCs proliferation was determined by MTT, while its effect on cell differentiation was analyzed using ALPase activity, and further confirmed with ALP and DSPP mRNA and protein expression. Immunostaining revealed that HGF was found mainly in the cytoplasm of DPCs. RT-PCR analysis showed that both HGF and c-met were expressed from the DPCs. Exogenous addition of HGF enhanced proliferation and differentiation of DPCs by up-regulating CREB, ELK-1, and PPAR-γ. U0126, an ERK/MAPK inhibitor, inhibited the effects of HGF on DPCs. It was concluded that HGF stimulated both proliferation and differentiation of DPCs, at least partially through the ERK/MAPK pathway.