Effects of saxagliptin on proliferation, differentiation, and apoptosis of osteoblasts in high glucose environment

GUO Liyan; WANG Jinlan; TAN Yinling; CHEN Fulian; DONG Zhenhua

doi:10.3969/j.issn.1002-266X.2017.28.005

Abstract：Objective To investigate the effects of saxagliptin on the proliferation, differentiation, and apoptosis of osteoblasts in high glucose environment, so as to provide the theoretical basis for the selection of rational hypoglycemic agents for patients with diabetic osteoporosis.Methods Osteoblasts MC3T3-E1 were cultured and passaged in a-MEM medium.The cells of 3 generations in the logarithmic phase were randomly divided into the normal control group, high glucose group, and high glucose + saxagliptin group.The a-MEM medium was immediately replaced with 5.5 mmol/L glucose medium in the normal control group, the a-MEM medium was immediately replaced with 30.0 mmol/L glucose medium in the high glucose group, and the a-MEM medium was immediately replaced with 30.0 mmol/L glucose +1 μmol/L saxagliptin medium in the high glucose + saxagliptin group.MC3T3-E1 osteoblasts were then cultured in different culture mediums for 48 h.CCK-8 method and flow cytometry were used to detect the proliferation ability and apoptosis rate, ELISA assay was used to detect alkaline phosphatase (ALP) activity, and qRT-PCR was used to detect the mRNA expression of COL-Ⅰ, Runx2, OCN and OPN.Results Compared with the normal control group, the proliferation, ALP activity and expression of COL-ⅠmRNA, Runx2 mRNA, OCN mRNA, and OPN mRNA were significantly decreased, and the apoptosis rate was significantly increased in the high glucose group and high glucose + saxagliptin group (all P<0.05).Compared with the high glucose group, the proliferation, ALP activity and expression of COL-ⅠmRNA, Runx2 mRNA, OCN mRNA, and OPN mRNA were significantly increased, and the apoptosis rate was significantly decreased in the high glucose + saxagliptin group (all P<0.05).Conclusion Saxagliptin can reverse the effects of high glucose environment on proliferation, differentiation, and apoptosis of MC3T3-E1 osteoblasts to a certain extent, which can be used for hypoglycemic therapy for patients with diabetic osteoporosis.