Abstract： Objective To investigate the effect of extracellular signal-regulated kinase(ERK) signaling pathway on the endothelial differentiation of periodontal ligament stem cells(PDLSC).Methods Human PDLSC was cultured in the medium with vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b-FGF) to induce endothelial differentiation.Endothelial inducing cells was incubated with U0126,a specific p-ERK1/2 inhibitor.PDLSC from one person were randomly divided into four groups:control group,endothelial induced group,endothelial induced + DMSO group and endothelial induced+U0126 group.The protein expression of the p-EKR1/2 was analyzed by Western blotting at 0,1,3,6 and 12 hours during endonthelial induction.The mRNA expressions of CD31,VE-cadherin,and VEGF were detected by quantitative real-time reverse transcriptase polymerase chain reaction(qRT-PCR) after a 7-day induction.The proportion of CD3F to VE-cadherin+cells was identified by flow cytometry,and the ability of capillary-like tubes formation was detected by Matrigel assay after a 14-day induction.The measurement data were statistically analyzed.Results Phosphorylated ERK1/2 protein level in PDLSC was increased to 1.24±0.12 and 1.03±0.24 at 1 h and 3 h respectively,during the endothelial induction(P＜0.01).The mRNA expressions of CD31 and VEGF in induced+U0126 group were decreased to 0.09±0.18 and 0.49±0.17,which were both significantly different with those in induced group(P＜0.05).The proportion of CD31 + to VE-cadherin+ cells of induced+U0126 group were decreased to 5.22±0.85 and 3.56±0.87,which were both significantly different with those in induced group(P＜0.05).In Matrigel assay,the branching points,tube number and tube length were decreased to 7.0±2.7,33.5±6.4,and (15 951.0±758.1) pixels,which were all significantly different with those in induced group(P＜0.05).Conclusions The endothelial differentiation of PDLSC is positively regulated by ERK signaling pathway.Inhibition of ERK1/2 phosphorylation could suppress endothelial differentiation of PDLSC.