Effects of sodium butyrate and 5-aza on differentiation of mesenchymal stem cells into cardiomyocytes

Objective To investigate the effects of sodium butyrate(histone deacetylate inhibitor) and 5-aza(DNA demethylation inhibitor) on differentiation of rat bone marrow mesenchymal stem cells(BMSCs) into cardiomyocytes in vitro. Methods Rat bone marrow mesenchymal stem cells were isolated, cultured and identified. The second passage cells were divided into 4 groups,the concentration of sodium butyrate is 0mM,0.5mM, 1.0mM,2.0mM in each group respectively. Then the proliferation and apoptosis of the four groups were detected by MTT and flow cytometry.To study myocardial specific proteins in these groups after induction, the result was con?rmed by immunofluorescence and western blot.Then it studied the other four groups:the control group,5-aza,sodium butyrate,5-aza+butyrate.the myocardial specific protein was identified after four weeks. Results sodium butyrate inhibited cell proliferation at all tested concentrations in a dose-dependent manner.However,it had no effect on cell apoptosis.sodium butyrate and 5-aza could induce BMSCs into cardiomyocytes,The best effective concentration of sodium butyrate is 1mM,and it is more prone to induce the differentiation of BMSCs than 5-aza.In additon,it is the most effective in differentiation with 5-aza and butyrate. Conclusion Sodium butyrate can promote the differentiation of BMSCs into cardiomyocytes effectively,and it is more prone than 5-aza with sodium butyrate at 1mM.Besides,the co-culture group with 5-aza and sodium butyrate is the strongest capacity of cardiomyocyte-like cells differentiation,which shows a cross-talk between histone acetylation and DNA demethylation.In a effective induced range of concentration, sodium butyrate inhibited cell proliferation ,but it had rarely effect on apoptosis of BMSCs,its showed that it is low toxicity, which may lay the foundation for future clinical applications.