Effects of pioglitazone on MC3T3-E1 osteoblasts in high glucose condition and its mechanism

AIM To assess the effects of pioglitazone on MC3T3-E1 osteoblasts which were exposed to constant high glucose condition,and try to explore the possible mechanisms.METHODS The MC3T3-E1 osteoblasts cultured in vitro high glucose condition(22.5 mmol·L~(-1)) were divided into four groups(control group(without pioglitazon),pioglitazone 2.5,5 and 10μmol·L~(-1) group),and intervened with different concentrations of pioglitazone for 24 and 48 hours.The cell proliferation ability,cells apoptosis,the levels of osteocalcin and ALP and the transcription of PPARγ,Runx2,BMP-2 mRNA were tested.The relevance of the expression of PPARγand Runx2 with osteocalcin,ALP,BMP-2 was analyzed.RESULTS At the same intervening time,the MC3T3-E1 osteoblast proliferation ability,secretion levels of osteocalcin and ALP, expressions of Runx2 mRNA and BMP-2 mRNA in the pioglitazone groups were lower than the control group (P0.05).The apoptosis rates and expression of PPARγmRNA of the pioglitazone groups compared with the control group were significantly higher(P0.05).With the increasing concentrations of pioglitazone,cell proliferation ability,secretion levels of osteocalcin and ALP,expressions of Runx2 mRNA and BMP-2 mRNA decreased,while the apoptosis rates and expression of PPARγmRNA increased(P0.05).Compared with the intervention 24 hours,cell proliferation ability,secretion levels of osteocalcin and ALP,expressions of PPARγmRNA,Runx2 mRNA,BMP-2 mRNA of the same pioglitazone concentration groups in intervention 48 hours did not change or slightly increased.CONCLUSION Pioglitazone may damage osteoblasts in high glucose condition.Promoting PPARγexpression and inhibiting Runx2 expression may be one of the mechanisms.