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α-硫辛酸通过抗氧化作用和PI3K/Akt信号通路减轻高糖对MC3T3-E1细胞成骨分化的抑制

Alpha-Lipoic Acid Alleviates High-Glucose Suppressed Osteogenic Differentiation of MC3T3-E1 Cells via Antioxidant Effect and PI3K/Akt Signaling Pathway.

作者信息

Dong Kai, Hao Pengjie, Xu Sheng, Liu Shutai, Zhou Wenjuan, Yue Xilong, Rausch-Fan Xiaohui, Liu Zhonghao

机构信息

Department of Dental Implantology, Yantai Stomatological Hospital, Shandong, China.

Department of Stomatology, Medical University of Vienna, Vienna, Austria.

出版信息

Cell Physiol Biochem. 2017;42(5):1897-1906. doi: 10.1159/000479605. Epub 2017 Aug 3.

Abstract

BACKGROUND/AIMS: Patients with diabetes mellitus have a higher risk of dental implant failure. One major cause is high-glucose induced oxidative stress. Alpha-lipoic acid (ALA), a naturally occurring compound and dietary supplement, has been established as a potent antioxidant that is a strong scavenger of free radicals. However, few studies have yet investigated the effect of ALA on osteogenic differentiation of osteoblasts cultured with high glucose medium. The aim of this study is to investigate the effects of ALA on the osteoblastic differentiation in MC3T3-E1 cells under high glucose condition.

METHODS

MC3T3-E1 cells were divided into 4 groups including normal glucose (5.5 mM) group (control), high glucose (25.5 mM) group, high glucose + 0.1 mM ALA group, and high glucose + 0.2 mM ALA group. The proliferation, osteogenic differentiation and mineralization of cells were evaluated by MTT assay, alkaline phosphatase (ALP) activity assay, alizarin red staining and real time-polymerase chain reaction. High-glucose induced oxidative damage was also assessed by the production of reactive oxygen species (ROS) and superoxide dismutase (SOD). Western blots were performed to examine the role of PI3K/Akt pathway.

RESULTS

The proliferation, osteogenic differentiation and mineralization of MC3T3-E1 cells were significantly decreased by the ROS induced by high-glucose. All observed oxidative damage and osteogenic dysfunction induced were inhibited by ALA. Moreover, the PI3K/Akt pathway was activated by ALA.

CONCLUSIONS

We demonstrate that ALA may attenuate high-glucose mediated MC3T3-E1 cells dysfunction through antioxidant effect and modulation of PI3K/Akt pathway.

摘要

背景/目的:糖尿病患者发生牙种植失败的风险更高。一个主要原因是高糖诱导的氧化应激。α-硫辛酸(ALA)是一种天然存在的化合物和膳食补充剂,已被确认为一种有效的抗氧化剂,是自由基的强力清除剂。然而,很少有研究探讨ALA对在高糖培养基中培养的成骨细胞成骨分化的影响。本研究的目的是探讨ALA在高糖条件下对MC3T3-E1细胞成骨分化的影响。

方法

将MC3T3-E1细胞分为4组,包括正常葡萄糖(5.5 mM)组(对照组)、高糖(25.5 mM)组、高糖+0.1 mM ALA组和高糖+0.2 mM ALA组。通过MTT法、碱性磷酸酶(ALP)活性测定、茜素红染色和实时聚合酶链反应评估细胞的增殖、成骨分化和矿化。还通过活性氧(ROS)和超氧化物歧化酶(SOD)的产生评估高糖诱导的氧化损伤。进行蛋白质免疫印迹法以检测PI3K/Akt信号通路的作用。

结果

高糖诱导的ROS显著降低了MC3T3-E1细胞的增殖、成骨分化和矿化。ALA抑制了所有观察到的氧化损伤和成骨功能障碍。此外,ALA激活了PI3K/Akt信号通路。

结论

我们证明,ALA可能通过抗氧化作用和调节PI3K/Akt信号通路减轻高糖介导的MC3T3-E1细胞功能障碍。

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