title: O-GlcNAcylation: a bridge between glucose and cell differentiation.
abstract: Glucose is the major energy supply and a critical metabolite for most cells and is especially important when cell is differentiating. High or low concentrations of glucose enhances or inhibits the osteogenic, chondrogenic and adipogenic differentiation of cell via the insulin, transforming growth factor-β and peroxisome proliferator-activated receptor γ pathways, among others. New evidence implicates the hexosamine biosynthetic pathway as a mediator of crosstalk between glucose flux, cellular signalling and epigenetic regulation of cell differentiation. Extracellular glucose flux alters intracellular O-GlcNAcylation levels through the hexosamine biosynthetic pathway. Signalling molecules that are important for cell differentiation, including protein kinase C, extracellular signal-regulated kinase, Runx2, CCAAT/enhancer-binding proteins, are modified by O-GlcNAcylation. Thus, O-GlcNAcylation markedly alters cell fate during differentiation via the post-transcriptional modification of proteins. Furthermore, O-GlcNAcylation and phosphorylation show complex interactions during cell differentiation: they can either non-competitively occupy different sites on a substrate or competitively occupy a single site or proximal sites. Therefore, the influence of glucose on cell differentiation via O-GlcNAcylation offers a potential target for controlling tissue homoeostasis and regeneration in ageing and disease. Here, we review recent progress establishing an emerging relationship among glucose concentration, O-GlcNAcylation levels and cell differentiation.
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shang
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Center for Evidence-based and Translational Medicine, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Minghan
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000215:Acylation; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D017351:N-Acetylglucosaminyltransferases; D011493:Protein Kinase C; D005947:Glucose; D000117:Acetylglucosamine
keywords: O-GlcNAcylation; adipogenic differentiation; cell differentiation; chondrogenic differentiation; glucose; osteogenic differentiation