title: High glucose microenvironments inhibit the proliferation and migration of bone mesenchymal stem cells by activating GSK3β.
abstract: 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.
authors.affiliation: Stomatology Department, General Hospital of Chinese PLA, 28 FuXing Road, Beijing, 100853, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Stomatology Department, General Hospital of Chinese PLA, 28 FuXing Road, Beijing, 100853, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Technical Institute of Physics and Chemistry of CAS, Beijing, China.
authors.forename: Haigang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Stomatology Department, General Hospital of Chinese PLA, 28 FuXing Road, Beijing, 100853, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Stomatology Department, General Hospital of Chinese PLA, 28 FuXing Road, Beijing, 100853, China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Stomatology Department, General Hospital of Chinese PLA, 28 FuXing Road, Beijing, 100853, China.
authors.forename: Huixia
authors.initials: H
authors.lastname: He
authors.affiliation: Stomatology Department, General Hospital of Chinese PLA, 28 FuXing Road, Beijing, 100853, China. gubin000@sina.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Gu
authors.affiliation: Stomatology Department, General Hospital of Chinese PLA, 28 FuXing Road, Beijing, 100853, China. liuhcpla@gmail.com.
authors.forename: Hongchen
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D060833:Cellular Microenvironment / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051821:Lymphoid Enhancer-Binding Factor 1; D019718:Receptors, CXCR4; D051176:beta Catenin; D019938:Cyclin D1; D000071679:Glycogen Synthase Kinase 3 beta; D005947:Glucose
keywords: GSK3β; High glucose; SDF-1/CXCR-4 axis; Stem cells
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