Abstract: Objective To investigate the effect of risperidone on the apoptosis of human osteoblast cell line hFob1.19 and analyze potential molecular mechanism based on Wnt/β-catenin signaling pathway. Methods hFob1.19 cells were divided into control group and risperidone intervention group (0, 5, 20, 40, 60, 80, 100 and 120 μmol/L). Cell viability was detected by CCK-8 assay. The apoptosis rate was detected by flow cytometry. RT-qPCR and Western blot was used to detect the mRNA and protein expression of BCL-2, MCL-1, BAX, and β-catenin. Results 1)Compared with the control group, the cell viability of the risperidone group decreased in a dose- and time-dependent manner (P＜0.05), while the apoptosis rate increased in a dose-dependent manner(P＜0.05). 2)Compared with the control group, the expression of pro-apoptotic gene BAX in risperidone group increased, while the expression of anti-apoptotic genes BCL-2 and MCL-1 decreased, and the expression of β-catenin decreased (P＜0.01). 3)Compared with the control group, the levels of pro-apoptotic proteins BAX and cleaved caspase-3 were increased, the levels of anti-apoptotic proteins BCL-2 and MCL-1 were decreased, and the expression of β-catenin protein was decreased in risperidone group (P＜0.01). 4) Compared with the control group, the expression of β-catenin protein in the nucleus and cytoplasm of risperidone group decreased (P＜0.05). Conclusions Risperidone induces apoptosis of hFob1.19 cells, and the mechanism may be related to the inhibition of β-catenin expression and nuclear translocation of β-catenin by risperidone, which leads to the disruption of the balance between anti-apoptotic and pro-apoptotic proteins.

Key words: risperidone, osteoblasts, apoptosis proteins, β-catenin