Protective effect of metformin on glucotoxicity in mouse cranium osteoblasts

AIM To investigate the effects of metformin on the high glucose-induced impairment on proliferation,apoptosis and expression of functional protein in osteoblasts.METHODS Mouse cranium osteoblasts were cultured in vitro and divided into normal glucose group(5.5 mmol·L~(-1)),high glucose group (25 mmol·L~(-1)),and low,middle,high metformin group(25 mmol·L~(-1) glucose + 25,50 or 100μmol·L~(-1) metformin,respectively).The cells were intervened for 48 and 72 hours.The cell proliferation ability was determined by MTT assay,and the cell apoptosis rate was detected by flow cytometry.Culture medium for bone formation was added into each group,and the intervention time was extended to 1,2 and 3 weeks. Chromatometry and RIA were used to determine the secretion levels of alkaline phosphatase(ALP) and osteocalcin(OCN),respectively.RESULTS At the same intervention time,compared with the normal glucose group,the high glucose group showed lower cell proliferation rate and higher early apoptosis rate(P0.05). With the increasing concentration of metformin,the proliferation rate of osteoblasts was increased(P0.05), and the apoptosis rate was decreased(P0.05).Prolonged the intervention time from 48 to 72 hours,the proliferation and early apoptosis rate of cells were increased in all groups.When the intervention time was extended to 1,2 and 3 weeks,the secretion levels of ALP and OCN were increased in the normal glucose group (P0.05),while decreased in the high glucose group.At the same intervention time,the secretion levels of ALP and OCN were increased with the increasing concentration of metformin(P0.05).CONCLUSION Metformin could protect against high glucose-induced cytotoxicity and improve the bone-formation capacity of osteoblasts in a dose-dependent manner.