Effect of XCT790 on MSCs apoptosis induced by serum deprivation，hypoxia and high glucose concentration

Abstract:

Objective：To investigate the effects of XCT790 on bone mesenchymal stem cells（MSCs） apoptosis induced by hypoxia，serum deprivation and high glucose concentration. Methods：MSCs were divided into 5 groups：control group（cultrued under normal conditions） and 0-20 μmol/L XCT790 treatment groups（cultured under 3％ O2，serum deprivation and 25 mmol/L glucose concentra－tion）. The apoptosis rates were measured by Annexin V-APC /7-AAD on flow cytometry. The protein levels of Bcl-2 and Bax corre－lated with apoptosis were detected by Western blot. And the ratios of Bcl-2/Bax were calculated. Results：After being exposed to 5-20 μmol/L XCT790 for 24 h，the apoptosis rates of 5 μmol/L XCT790 treatment group（20.02±0.92）%，10 μmol/L XCT790 treatment group（26.04±1.24）% and 20 μmol/L XCT790 treatment group（50.73±3.55）% were significantly higher than of 0 μmol/L XCT790 treatment group（14.34±0.61）%，increasing in a dose-dependent manner（P<0.05）. Western blot showed the expression of pro-apop－totic protein Bax in 5 μmol/L XCT790 treatment group（0.132 3±0.033 8），10 μmol/L XCT790 treatment group（0.140 8±0.006 8） and 20 μmol/L XCT790 treatment group（0.199 4±0.061 7） was significantly higher than that in 0 μmol/L treatment group（0.116 4±0.017 2），while the expression of anti-apoptotic protein Bcl-2 in 5 μmol/L XCT790 treatment group（0.069 7±0.013 2），10 μmol/L XCT790 treatment group（0.051 2±0.005 6），20 μmol/L treat－ment group（0.041 3±0.005 5） was significantly lower than that in 0 μmol/L treatment group（0.092 3±0.021 3）. The Bcl-2/Bax ratios of 5 μmol/L XCT790 treatment group（0.530 7±0.027 9），10 μmol/L XCT790 treatment group（0.397 9±0.034 2） and 20 μmol/L XCT790 treatment group（0.234 8±0.032 1） were significantly lower than that in 0 μmol/L XCT790 treatment group（0.851 7±0.084 4），decreasing in a dose dependent manner（P<0.05）. Conclusion：In the conditions of hypoxia，serum deprivation and high glucose concentration，antagonism of estrogen-related receptor α makes MSCs apoptosis rates increase significantly as Bcl-2/Bax ratios decrease，which indicates that ERRα plays an important role in preventing MSCs apoptosis.