title: Different concentrations of glucose regulate proliferation and osteogenic differentiation of osteoblasts via the PI3 kinase/Akt pathway.
abstract: BACKGROUND
  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.
authors.affiliation: *PhD Student, Department of Implant Dentistry, School of Stomatology, Shandong University, Jinan, China; Chief Physician, Department of Dental Implantology, Yantai Stomatological Hospital, Yantai, China. †Resident Physician, Department of Dental Implantology, Yantai Stomatological Hospital, Yantai, China. ‡Associate Chief Physician, Department of Dental Implantology, Yantai Stomatological Hospital, Yantai, China. §Professor, Department of Stomatology, Medical University of Vienna, Vienna, Austria. ‖Professor, Department of Implant Dentistry, School of Stomatology, Shandong University, Jinan, China.
authors.forename: Zhonghao
authors.initials: Z
authors.lastname: Liu
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Jiang
authors.forename: Kai
authors.initials: K
authors.lastname: Dong
authors.forename: Shutai
authors.initials: S
authors.lastname: Liu
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Meng
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Rausch-Fan
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D051379:Mice; D051058:Oncogene Protein v-akt / Q000502:physiology*; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D000469:Alkaline Phosphatase; D005947:Glucose