不同浓度的葡萄糖通过PI3激酶/蛋白激酶B信号通路调节成骨细胞的增殖和骨生成分化。
Different concentrations of glucose regulate proliferation and osteogenic differentiation of osteoblasts via the PI3 kinase/Akt pathway.
作者信息
Liu Zhonghao, Jiang Huanhuan, Dong Kai, Liu Shutai, Zhou Wenjuan, Zhang Jing, Meng Lei, Rausch-Fan Xiaohui, Xu Xin
机构信息
*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.
出版信息
Implant Dent. 2015 Feb;24(1):83-91. doi: 10.1097/ID.0000000000000196.
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.
引言
本研究旨在探讨高糖水平对MC3T3-E1成骨细胞系增殖和成骨能力的影响，并探究磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（Akt）信号通路的调控机制。
方法
将培养物分为8个处理组：4种葡萄糖浓度（5.5、15.5、25.5和35.5 mM），分别添加或不添加LY294002。分析细胞增殖、碱性磷酸酶（ALP）检测、矿化结节的茜素红染色、成骨基因和磷酸化Akt（P-AKT）表达。
结果
当葡萄糖浓度从5.5 mM变化至15.5 mM时，MC3T3-E1细胞的增殖、ALP活性、矿化、成骨基因（RUNX2、OSX、OPN、OCN）和P-AKT表达均增加。然而，当葡萄糖浓度继续从25.5 mM升高至35.5 mM时，MC3T3-E1细胞的增殖和成骨能力逐渐下降。此外，在葡萄糖浓度为15.5 mM（最佳浓度）时，PI3K/Akt抑制剂LY294002显著抑制了这些效应。
结论
适当的高糖浓度（15.5 mM）可通过激活MC3T3-E1细胞中的PI3K/Akt通路增加成骨分化，但过高的葡萄糖浓度（25.5和35.5 mM）会抑制生物矿化过程。研究结果表明，PI3K/Akt通路在MC3T-E1细胞的生理过程中起重要作用。
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