Objective To explore the effect and its mechanism of esketamine on the proliferation and differentiation of osteoblasts.Methods Osteoblasts were extracted and transformed from C57B 1/6 male mice.The toxicity of different concentrations(0,6.25,12.5,25,50,100,200 µmol/L)of N-methyl-D-aspartic acid(NMDA)for 24,48,72,96 h to osteoblasts was detected by cell counting kit-8(CCK-8)method to screen the appropriate concentration.The induced osteoblasts were divided into three groups:control group,esketamine(Ket)group and Ket+NMDA group.After 24,48,72 h intervention,the mRNA expression levels of Runt associated tran-scription factor 2(Runx2)and the osteoblast specific transcription factor Osterix in each group were detected by real-time fluorescence quantitative PCR(qPCR),and the expression levels of B-lymphoblastoma-2 gene(Bcl-2),Bcl-2-associated X gene(Bax)and brain-derived neurotrophic factor(BDNF)proteins in osteoblasts in each group were determined by enzyme-linked immunosorbent assay(ELISA).Results CCK-8 results showed that 0-200 µmol/L NMDA had no obvious toxicity to osteoblast proliferation at the same time point(P＞0.05)and there was no significant difference in the activity of osteoblasts after NMDA intervention for different time(P＞0.05).The qPCR results showed that the expression levels of Runx2 and Osterix in Ket group and Ket+NMDA group were higher than those in control group(P＜0.01)and the expression levels of Runx2 and Osterix in Ket+NMDA group were lower than those in Ket group(P＜0.01).ELISA results showed that the expression levels of Bcl-2 protein and BDNF protein in Ket group were higher than those in control group,while the expression level of Bax protein was lower(all P＜0.05).Compared with Ket group,the expression levels of Bcl-2 protein and BDNF protein were decreased and Bax protein was increased in Ket+NMDA group(all P＜0.05).Conclusion Esketamine may promote the proliferation and differentiation of mouse osteoblasts by blocking N-methyl-D-aspartate receptor(NMDAR),which increases BDNF expression,thus increasing the expression of anti-apoptotic proteins while inhibiting the expression of apoptotic proteins.
维普
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