Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 cooperates with glycogen synthase kinase-3β to regulate osteogenesis of bone-marrow mesenchymal stem cells in type 2 diabetes. (15th January 2017)

• Record Type: Journal Article
• Authors: Li, Xiaoguang; Liu, Na; Wang, Yizhu; Liu, Jinglong; Shi, Haigang; Qu, Zhenzhen; Du, Tingting; Guo, Bin; Gu, Bin
• Is Part Of: Molecular and cellular endocrinology. Volume 440(2017)
• Page Start: 93
• Page End: 105
• Publication Date: 2017-01-15
• Subjects: Bone marrow mesenchymal stem cells -- Osteogenic differentiation -- Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 -- Glycogen synthase kinase-3β -- Type 2 diabetes mellitus; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.10.001
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: 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 β-catenin and T cell factor (TCF) expression were decreased, the glycogen synthase kinase-3β (GSK-3β) 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/β-catenin pathway, which was partially due to inhibition of GSK-3β 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-3β expression to activate Wnt/β-catenin pathway. BMAL1 may have a potential use in repairing diabetic bone metabolic disorders. Graphical abstract: Highlights: BMSCs osteogenesis is suppressed along with reduced BMAL1 and activated GSK3β in T2DM. BMAL1 downregulation inhibits Wnt/β-catenin pathway mainly via enhanced GSK3β in BMSCs. BMAL1 overexpression inhibits GSK-3β resulting in activation of Wnt/β-catenin pathway. GSK3β inhibition has a synergistic effect with overexpression of BMAL1 in GK BMSCs. Up-regulation of BMAL1 can recover the inhibited osteogenesis of BMSCs in T2DM.