SIRT6 overexpression inhibits cementogenesis by suppressing glucose transporter 1
SIRT6 overexpression inhibits cementogenesis by suppressing glucose transporter 1
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SIRT6 过表达通过抑制葡萄糖转运蛋白 1 抑制牙骨质形成
DOI：
10.1002/jcp.27213
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发表时间：
2019-04-01
影响因子：
5.6
通讯作者：
Huang, Cui
中科院分区：
文献类型：
--
作者：
Huang, Liyuan;Sun, Hualing;Huang, Cui
在牙周炎和正畸治疗过程中，牙骨质与骨具有共同的生化组成特征，对牙周组织的稳态至关重要。Sirtuin 6 （SIRT6）作为Sirtuin家族的一员，在骨髓间充质干细胞的成骨分化中起关键作用。然而，SIRT6参与成水泥细胞分化和矿化及其潜在机制尚不清楚。在这项研究中，我们观察到SIRT6的表达在成水泥细胞分化初期增加。功能增益和功能损失分析表明，OCCM - 30细胞中过表达SIRT6抑制成水泥细胞分化和矿化，下调SIRT6促进水泥生成。GLUT1是胶凝形成中必需的葡萄糖转运蛋白，它被SIRT6抑制。在SIRT6 -过表达的OCCM - 30细胞中过表达GLUT1恢复了SIRT6对成水泥细胞分化和矿化的抑制作用。此外，AMPK在过表达SIRT6后被激活，抑制成水泥细胞分化和矿化。下调SIRT6的表达可抑制AMPK活性。同时，GLUT1过表达显著降低AMPK活性。总的来说，一方面，SIRT6通过抑制GLUT1抑制成水泥细胞分化和矿化。另一方面，SIRT6通过激活AMPK通路抑制成水泥细胞分化和矿化。GLUT1过表达也挽救了SIRT6激活的AMPK通路的增加。
Cementum, which shares common features with bone in terms of biochemical composition, is important for the homeostasis of periodontium during periodontitis and orthodontic treatment. Sirtuin 6 (SIRT6), as a member of the sirtuin family, plays key roles in the osteogenic differentiation of bone marrow mesenchymal stem cells. However, the involvement of SIRT6 in cementoblast differentiation and mineralization and the underlying mechanisms remain unknown. In this study, we observed that the expression of SIRT6 increased during cementoblast differentiation initially. Analysis of the gain‐ and loss‐of‐function indicated that overexpressing SIRT6 in OCCM‐30 cells suppresses cementoblast differentiation and mineralization and downregulating SIRT6 promotes cementogenesis. GLUT1, a glucose transporter necessary in cementogenesis, was inhibited by SIRT6. Overexpressing GLUT1 in SIRT6‐overexpressed OCCM‐30 cells rescued the inhibitory effect of SIRT6 on cementoblast differentiation and mineralization. Moreover, AMPK was activated after overexpressing SIRT6 and inhibited cementoblast differentiation and mineralization. Downregulating the expression of SIRT6 inhibited AMPK activity. Meanwhile, GLUT1 overexpression significantly decreased AMPK activity. Overall, on one hand, SIRT6 inhibited cementoblast differentiation and mineralization by suppressing GLUT1. On the other hand, SIRT6 inhibited cementoblast differentiation and mineralization by activating the AMPK pathway. GLUT1 overexpression also rescued the increased AMPK pathway activated by SIRT6.