title: 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.
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.
authors.affiliation: Institution of Stomatology, The General Hospital of Chinese PLA, Beijing, China. Electronic address: xiaopa3084@126.com.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
authors.affiliation: Institution of Stomatology, The General Hospital of Chinese PLA, Beijing, China. Electronic address: liuna0216@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Institution of Stomatology, The General Hospital of Chinese PLA, Beijing, China. Electronic address: 17701308150@163.com.
authors.forename: Yizhu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institution of Stomatology, The General Hospital of Chinese PLA, Beijing, China. Electronic address: summer_mimosa@hotmail.com.
authors.forename: Jinglong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, China. Electronic address: 402926405@qq.com.
authors.forename: Haigang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Stomatology, Beijing Xinhua Hospital, Beijing, China. Electronic address: quzhenzhen2008@126.com.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Institution of Stomatology, The General Hospital of Chinese PLA, Beijing, China. Electronic address: 251697011@qq.com.
authors.forename: Tingting
authors.initials: T
authors.lastname: Du
authors.affiliation: Institution of Stomatology, The General Hospital of Chinese PLA, Beijing, China. Electronic address: guobin0408@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.affiliation: Institution of Stomatology, The General Hospital of Chinese PLA, Beijing, China. Electronic address: gubmail@gmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Gu
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis; D051381:Rats; D060449:Wnt Signaling Pathway
chemical_list: D056930:ARNTL Transcription Factors; C000598703:Arntl protein, rat; D015415:Biomarkers; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Bone marrow mesenchymal stem cells; Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1; Glycogen synthase kinase-3β; Osteogenic differentiation; Type 2 diabetes mellitus