title: Hexosamine-Induced TGF-β Signaling and Osteogenic Differentiation of Dental Pulp Stem Cells Are Dependent on N-Acetylglucosaminyltransferase V.
abstract: Glycans of cell surface glycoproteins are involved in the regulation of cell migration, growth, and differentiation. N-acetyl-glucosaminyltransferase V (GnT-V) transfers N-acetyl-d-glucosamine to form β1,6-branched N-glycans, thus playing a crucial role in the biosynthesis of glycoproteins. This study reveals the distinct expression of GnT-V in STRO-1 and CD-146 double-positive dental pulp stem cells (DPSCs). Furthermore, we investigated three types of hexosamines and their N-acetyl derivatives for possible effects on the osteogenic differentiation potential of DPSCs. Our results showed that exogenous d-glucosamine (GlcN), N-acetyl-d-glucosamine (GlcNAc), d-mannosamine (ManN), and acetyl-d-mannosamine (ManNAc) promoted DPSCs' early osteogenic differentiation in the absence of osteogenic supplements, but d-galactosamine (GalN) or N-acetyl-galactosamine (GalNAc) did not. Effects include the increased level of TGF-β receptor type I, activation of TGF-β signaling, and increased mRNA expression of osteogenic differentiation marker genes. The hexosamine-treated DPSCs showed an increased mineralized matrix deposition in the presence of osteogenic supplements. Moreover, the level of TGF-β receptor type I and early osteogenic differentiation were abolished in the DPSCs transfected with siRNA for GnT-V knockdown. These results suggest that GnT-V plays a critical role in the hexosamine-induced activation of TGF-β signaling and subsequent osteogenic differentiation of DPSCs.
authors.affiliation: Department of Dentistry, National Taiwan University Hospital and School of Dentistry, National Taiwan University, Taipei City 10048, Taiwan.
authors.forename: Yi-Jane
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Dentistry, National Taiwan University Hospital and School of Dentistry, National Taiwan University, Taipei City 10048, Taiwan.
authors.forename: Chung-Chen
authors.initials: CC
authors.lastname: Yao
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei City 10048, Taiwan.
authors.forename: Chien-Hsun
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Dentistry, National Taiwan University Hospital and School of Dentistry, National Taiwan University, Taipei City 10048, Taiwan.
authors.forename: Hao-Hueng
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei City 10048, Taiwan.
authors.forename: Tai-Horng
authors.initials: TH
authors.lastname: Young
mesh_terms: D000117:Acetylglucosamine / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005944:Glucosamine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006595:Hexosamines / Q000008:administration & dosage; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D055815:Young Adult
chemical_list: D006595:Hexosamines; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C008322:mannosamine; C035547:glucosaminic acid; C000601122:Mgat5 protein, human; D017351:N-Acetylglucosaminyltransferases; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D005944:Glucosamine; D000117:Acetylglucosamine