Chen Yi-Jane, Yao Chung-Chen, Huang Chien-Hsun, Chang Hao-Hueng, Young Tai-Horng
Department of Dentistry, National Taiwan University Hospital and School of Dentistry, National Taiwan University, Taipei City 10048, Taiwan.
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei City 10048, Taiwan.
Biomed Res Int. 2015;2015:924397. doi: 10.1155/2015/924397. Epub 2015 Oct 25.
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.
细胞表面糖蛋白的聚糖参与细胞迁移、生长和分化的调控。N-乙酰葡糖胺基转移酶V（GnT-V）转移N-乙酰-d-葡糖胺以形成β1,6分支的N-聚糖，从而在糖蛋白的生物合成中发挥关键作用。本研究揭示了GnT-V在STRO-1和CD-146双阳性牙髓干细胞（DPSC）中的不同表达。此外，我们研究了三种己糖胺及其N-乙酰衍生物对DPSC成骨分化潜能的可能影响。我们的结果表明，在没有成骨补充剂的情况下，外源性d-葡糖胺（GlcN）、N-乙酰-d-葡糖胺（GlcNAc）、d-甘露糖胺（ManN）和乙酰-d-甘露糖胺（ManNAc）促进了DPSC的早期成骨分化，但d-半乳糖胺（GalN）或N-乙酰半乳糖胺（GalNAc）则没有。其作用包括I型TGF-β受体水平的增加、TGF-β信号的激活以及成骨分化标记基因mRNA表达的增加。在有成骨补充剂存在的情况下，经己糖胺处理的DPSC显示矿化基质沉积增加。此外，在用针对GnT-V敲低的siRNA转染的DPSC中，I型TGF-β受体水平和早期成骨分化被消除。这些结果表明，GnT-V在己糖胺诱导的TGF-β信号激活以及随后的DPSC成骨分化中起关键作用。
