Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 cooperates with glycogen synthase kinase-3 beta to regulate osteogenesis of bone-marrow mesenchymal stem cells in type 2 diabetes

作者：Li, Xiaoguang; Liu, Na; Wang, Yizhu; Liu, Jinglong; Shi, Haigang; Qu, Zhenzhen; Du, Tingting; Guo, Bin^*; Gu, Bin^*

来源：Molecular and Cellular Endocrinology, 2017, 440(C): 93-105.

DOI：10.1016/j.mce.2016.10.001

• Bone marrow mesenchymal stem cells
• Osteogenic differentiation
• Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1
• Glycogen synthase kinase-3 beta
• Type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is associated with inhibited osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Brain and muscle ARNT-like protein 1 (BMAL1) has been linked to the T2DM-related bone remodeling, however, the specific mechanism is still unclear. Herein, we aimed to determine the role of BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Inhibited osteogenesis and BMAL1 expression were showed in diabetic BMSCs. And while beta-catenin and T cell factor (TCF) expression were decreased, the glycogen synthase kinase-3 beta (GSK-3 beta) and nemo-like kinase (NLK) expression were increased in diabetic BMSCs. Moreover, over-expression of BMAL1 led to recovered osteogenesis ability and activation of Wnt/beta-catenin pathway, which was partially due to inhibition of GSK-3 beta caused by over-expression of BMAL1. Taken together, our findings provide new insights into the role of BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Over-expressed BMAL1 could recover BMSCs osteogenesis in T2DM partially by decreasing GSK-3 beta expression to activate Wnt/beta-catenin pathway. BMAL1 may have a potential use in repairing diabetic bone metabolic disorders.

• 出版日期2017-1-15
• 单位中国人民解放军总医院; 中国科学院理化技术研究所