Role of HDAC2 in the osteogenic differentiation of bone marrow mesenchymal stem cells exposed to high glucose / 实用医学杂志

ABSTRACT

Objective To investigate the relationship between diabetes and bone metabolism and the potential epigenetic mechanisms. Methods BMSCs were cultured for 7 and 15 days in cell culture medium with different concentrations of glucose. The mRNA and protein expression of HDACs and osteogenesis-related genes were detected by RT-PCR and Western blot assay ,respectively. Moreover ,the combination of HDAC to the promoter region of Runx2 was tested by the chromatin immunoprecipitation (ChIP) assay. Results ThemRNA expression of osteogenesis-related genes ,incuding OCN(P < 0.05)and Col1(P < 0.05),in the bone marrow of diabetic mice was significantly reduced compared with the control mice. The mRNA and protein expression of ALP ,OCN ,Runx2 and OSX was gradually reduced with the increasing concentration of glucose ,while HDAC2 mRNA and protein expression was increased. The binding activity of HDAC2 to the upstream and downstream of Runx2 promoter region in 25mM glucose-treated BMSCs was higher than the control group(P < 0.05). Conclusoins Diabetes might repress osteogenesis of BMSCs via inhibiting the activity of Runx2 through upregu-lating the expression of HDAC2.