Zhang Bo, Liu Na, Shi Haigang, Wu Hao, Gao Yuxuan, He Huixia, Gu Bin, Liu Hongchen
Stomatology Department, General Hospital of Chinese PLA, 28 FuXing Road, Beijing, 100853, China.
Technical Institute of Physics and Chemistry of CAS, Beijing, China.
J Bone Miner Metab. 2016 Mar;34(2):140-50. doi: 10.1007/s00774-015-0662-6. Epub 2015 Apr 4.
Diabetes mellitus involves metabolic changes that can impair bone repair. Bone mesenchymal stem cells (BMSCs) play an important role in bone regeneration. However, the bone regeneration ability of BMSCs is inhibited in high glucose microenvironments. It can be speculated that this effect is due to changes in BMSCs' proliferation and migration ability, because the recruitment of factors with an adequate number of MSCs and the microenvironment around the site of bone injury are required for effective bone repair. Recent genetic evidence has shown that the Cyclin D1 and the CXC receptor 4 (CXCR-4) play important roles in the proliferation and migration of BMSCs. In this study we determined the specific role of glycogen synthase kinase-3β (GSK3β) in the proliferation and migration of BMSCs in high glucose microenvironments. The proliferation and migration ability of BMSCs were suppressed under high glucose conditions. We showed that high glucose activates GSK3β but suppresses CXCR-4, β-catenin, LEF-1, and cyclin D1. Inhibition of GSK3β by LiCl led to increased levels of β-catenin, LEF-1, cyclin D1, and CXCR-4 expression. Our data indicate that GSK3β plays an important role in regulating the proliferation and migration of BMSCs by inhibiting cyclin D1 and CXCR-4 under high glucose conditions.
糖尿病涉及可损害骨修复的代谢变化。骨间充质干细胞（BMSCs）在骨再生中起重要作用。然而，在高糖微环境中，BMSCs的骨再生能力受到抑制。可以推测，这种效应是由于BMSCs增殖和迁移能力的变化，因为有效的骨修复需要募集足够数量的间充质干细胞以及骨损伤部位周围的微环境。最近的遗传学证据表明，细胞周期蛋白D1和CXC趋化因子受体4（CXCR - 4）在BMSCs的增殖和迁移中起重要作用。在本研究中，我们确定了糖原合酶激酶 - 3β（GSK3β）在高糖微环境中BMSCs增殖和迁移中的具体作用。在高糖条件下，BMSCs的增殖和迁移能力受到抑制。我们发现高糖激活GSK3β，但抑制CXCR - 4、β - 连环蛋白、淋巴样增强因子1（LEF - 1）和细胞周期蛋白D1。用氯化锂抑制GSK3β导致β - 连环蛋白、LEF - 1、细胞周期蛋白D1和CXCR - 4表达水平升高。我们的数据表明，在高糖条件下，GSK3β通过抑制细胞周期蛋白D1和CXCR - 4在调节BMSCs的增殖和迁移中起重要作用。
