期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 440, 期 C, 页码 93-105出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2016.10.001
关键词
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
资金
- National Natural Science Foundation of China [81470754, 51473175, 31670998]
- China Postdoctoral Science Foundation [2014T70959]
- Beijing Nova Program [Z141107001814101]
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. (C) 2016 Published by Elsevier Ireland Ltd.
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