Abstract: Objective To study the effect and mechanism of mitogen-activated protein kinase(MAPK)signal transduction pathway in nicotine-induced human periodontal ligament fibroblasts(PDLFs)apoptosis.Methods The PDLFs were treated with different doses of nicotine(1,10,and 100μg/mL).Twenty-four hours after the treatments,the expressions of JAK1,JAK2,MAPK,MAPKK,JNK,p38,and ERK were detected with reverse transcriptase polymersase chain reaction(RT-PCR)and the expression of caspase-3 was determined with western blot.Results After the treatments of 1,10 and 100μg/mL nicotine,the transcriptive expressions of the genes were 65.17±8.45,106.17±22.22,and 115.50±8.12 for JAK1,103.00±13.13,118.17±13.17,and 159.00±13.74 for JAK2,126.69±18.20,143.02±13.97,and 172.64±26.43 for MAPKK,79.17±4.49,115.67±7.66,and 122.33±8.41 for MAPKK,110.64±11.14,128.54±11.72,and 132.90±11.99 for p38,106.16±26.89,123.17±13.09,and 132.68±11.97 for JNK,131.52±19.85,144.76±13.87,and 153.59±13.85 for caspase-3,and 128.33±13.50,144.00±12.53,and 153.00±12.77 for caspase-3 translation,respectively.Compared with those of the control group,all the differences were statistically significant(P<0.05 or P<0.01 for all).The expressions of the genes showed a gradual increasing trend with the increment of nicotine dose,except the transcription of ERK.Conclusion Nicotine-induced PDLFs apoptosis may not be through the ERK-MAPK pathway but through p38-MAPK and JNK-MAPK pathway and nicotine could lead to the increase of caspase-3.