Hexosamine-Induced TGF-β Signaling and Osteogenic Differentiation of Dental Pulp Stem Cells Are Dependent on N-Acetylglucosaminyltransferase V.
Hexosamine-Induced TGF-β Signaling and Osteogenic Differentiation of Dental Pulp Stem Cells Are Dependent on N-Acetylglucosaminyltransferase V.
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DOI：
10.1155/2015/924397
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发表时间：
2015
影响因子：
--
通讯作者：
Young TH
中科院分区：
文献类型：
--
作者：
Chen YJ;Yao CC;Huang CH;Chang HH;Young TH
细胞表面糖蛋白的聚糖参与细胞迁移、生长和分化的调节。N-乙酰氨基葡萄糖转移酶V（GnT-V）是将N-乙酰氨基葡萄糖转化为β 1，6-支链N-聚糖的酶，在糖蛋白的生物合成中起重要作用。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，我们研究了三种类型的己糖胺及其N-乙酰基衍生物对DPSCs成骨分化潜能的可能影响。我们的结果表明，外源性D-葡萄糖胺（GlcN），N-乙酰-D-葡萄糖胺（GlcNAc），D-甘露糖胺（ManN）和乙酰-D-甘露糖胺（ManNAc）促进DPSC的早期成骨分化，而D-半乳糖胺（GalN）或N-乙酰-半乳糖胺（GalNAc）没有。影响包括I型TGF-β受体水平增加、TGF-β信号传导激活和成骨分化标志物基因mRNA表达增加。己糖胺处理的DPSC显示在成骨补充剂存在下增加的矿化基质沉积。此外，在转染GnT-V敲低siRNA的DPSCs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信号转导激活和随后的DPSC成骨分化中起关键作用。
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.