Objective:This study aimed at the effect of tumor necrosis factor receptor-associated factor 6(TRAF6)knockdown on interleukin-17(IL-17)modulating the expression of osteoprotegerin(OPG)and receptor activator for nuclear factor-κB ligand(RANKL)in human periodontal ligament cells(hPDLCs)under hypoxia. Methods:The experiment was set as the normoxia plus IL-17 group,the hypoxia plus IL-17 group and the hypoxia group. Each group was divided into the negative control group(the TRAF6-NC group)and the disturbance group(the TRAF6-shRNA group). The shRNA lentiviral vector was used to infect hPDLCs. The efficiency of infection was observed by inverted microscope and verified by RT-PCR. The expression of HIF-1α,RANKL and OPG in human periodontal ligament cells were detected by Western blot and RT-PCR. Results:The ratio of RANKL/OPG relative expression of RANKL and OPG protein in the hypoxia plus IL-17 group was higher than that in the hypoxia group. Under hypoxia plus IL-17 conditions,the expression of RANKL was decreased in the TRAF6-shRNA group compared with the TRAF6-NC group,and the ratio of RANKL/OPG relative expression of RANKL and OPG was decreased. Conclusion:TRAF6 is involved in the regulation of IL-17-stimulated expression of bone resorption molecules in human periodontal ligament cells in hypoxic conditions. Knocking down TRAF6 can reduce IL-17-induced expression of bone resorption molecules in human periodontal ligament cells.