Hexosamine-Induced TGF-β Signaling and Osteogenic Differentiation of Dental Pulp Stem Cells Are Dependent on N-Acetylglucosaminyltransferase V

Abstract EN

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.