Advances in Clinical and Experimental Medicine
Ahead of print
Publication type: original article
Notch pathway activation promotes the differentiation of beagle dog periodontal ligament stem cells to Schwann cells
1 Department of Dentistry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, China
2 Department of Dentistry, The Second Affiliated Hospital, Zhejiang University School of Medicine, China
Background. Periodontal ligament stem cells (PDLSCs) have demonstrated the potential for differentiation into many cell types, though the molecular mechanism of their neural differentiation in particular remains largely unknown.
Objectives. The Notch signaling pathway plays a key role in regulating cell differentiation and development. In this article, we explore its potential role in the differentiation of PDLSCs to Schwann cells (SCs).
Material and Methods. The PDLSCs were either transfected with viral vectors carrying genetic material for Notch Delta ligands, thereby induced their overexpression, or treated with DAPT (a Notch-pathway-specific inhibitor) to inhibit γ-secretase. The potential effects of Notch signaling on myelination and SCs differentiation were then investigated using western blotting, immunostaining and reverse transcriptase polymerase chain reaction (RT-PCR) to detect the expression of SC-specific marker genes.
Results. Specifically inhibiting Notch signaling with DAPT decreased the expression of SC-specific marker genes GFAP, S100 and P75, as well as of SC-myelin-related genes PMP22, MBP, connexin, and P0 in cells undergoing induced differentiation from PDLSCs. Conversely, activating Notch signaling through overexpression of Delta ligands enhanced the expression of SC-specific marker genes as well as myelin-related genes in cells undergoing induced differentiation from PDLSCs. This promotion was reversed by DAPT.
Conclusion. The Notch signaling pathway positively regulated the process of PDLSC differentiation into SCs, and the activation of this signaling was important in maintaining the differentiation of PDLSCs to SCs, and then SC myelination. These results may improve the method of obtaining pure SCs from PDLSCs for transplantation application.
differentiation, Schwann cells, periodontal ligament stem cells, Notch signaling pathway
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