Different Concentrations of Glucose Regulate Proliferation and Osteogenic Differentiation of Osteoblasts Via the PI3 Kinase/Akt Pathway

Introduction: The aim of this study was to investigate the effect of high glucose levels on proliferation and osteogenic ability in MC3T3-E1 osteoblastic cell line and to explore the regulatory mechanism of PI3 kinase (PI3K)/Akt signaling pathway. Methods: The cultures were divided into 8 treatment groups: 4 concentrations of glucose (5.5, 15.5, 25.5, and 35.5 mM) with or without LY294002. Cell proliferation, alkaline phosphatase (ALP) assay, alizarin red staining of mineralized nodule, osteogenic genes, and P-AKT expression were analyzed. Results: Cell proliferation, ALP activity, mineralization, osteogenic genes (RUNX2, OSX, OPN, OCN) and P-AKT expression in MC3T3-E1 cells were increased, whereas the glucose concentration changed from 5.5 to 15.5 mM. However, when the glucose concentrations continue to increase from 25.5 to 35.5 mM, the proliferation and osteogenic ability in MC3T3-E1 cells were gradually declined. Furthermore, these effects were significantly inhibited by PI3K/Akt inhibitor LY294002 at a glucose concentration of 15.5 mM, which was the optimum. Conclusions: Appropriate high glucose concentration (15.5 mM) can increase osteogenic differentiation by activating PI3K/Akt pathway in MC3T3-E1 cells, but exorbitant high glucose concentrations (25.5 and 35.5 mM) inhibited the biomineralization process. Findings indicated that PI3K/Akt pathway plays an important role in the physiological process of MC3T3-E1 cells.