2022, Vol. 26 ›› Issue (29): 4699-4703

Mechanism by which SC79, an Akt activator, inhibits dexamethasone-induced apoptosis and programmed necrosis of osteoblasts

Song Jianzhi, Xu Lisen, Zhang Chen, Tu Feng, Niu Fei   

Abstract: BACKGROUND: SC79 is an Akt activator that has a certain cytoprotective effect. It cannot only inhibit excitotoxicity, but also reduce neuronal cell death caused by stroke.
OBJECTIVE: To investigate the mechanism of SC79 inhibiting dexamethasone-induced apoptosis and programmed necrosis of osteoblasts.
METHODS: Human osteoblasts, OB-6 cells, in logarithmic growth phase were divided into four groups: normal culture group, dexamethasone group treated with 2 μmol/L dexamethasone for 24 hours, SC79 group treated with 20 μmol/L SC79 for 24 hours, and SC79+dexamethasone group treated with 20 μmol/L
SC79 for 2 hours and then 2 μmol/L dexamethasone for 24 hours. Cell activity, lactate dehydrogenase release, and apoptosis rate were detected. Activities of apoptosis-related factors Caspase-3, Bax, and Bcl-2, and the protein expression of oxidative stress-related factors cyclophilin D and cytochrome C were measured.
RESULTS AND CONCLUSION: Compared with the normal control group, the dexamethasone group significantly decreased cell activity (P < 0.05), increased lactate dehydrogenase release and mitochondrial membrane potential intensity (P < 0.05), elevated Caspase-3 and Bax activities and apoptosis rate (P < 0.05), decreased the expression of Bcl-2 protein (P < 0.05), and upregulated the expression levels of cyclophilin D and cytochrome C proteins (P < 0.05). Compared with the dexamethasone group, the SC79+dexamethasone group significantly increased cell activity (P < 0.05), reduced lactate dehydrogenase release and mitochondrial membrane potential intensity (P < 0.05), decreased Caspase-3 and Bax activities and apoptosis rate (P < 0.05), elevated the expression of Bcl-2 protein (P < 0.05), and downregulated the expression levels of cyclophilin D and cytochrome C proteins (P < 0.05). To conclude, SC79 can inhibit dexamethasone-induced apoptosis and programmed necrosis of osteoblasts by enhancing cell activity and inhibiting apoptosis, mitochondrial membrane potential and oxidative stress.
Key words: SC79, dexamethasone, osteoblast, apoptosis, programmed necrosis, mechanism