Abstract
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. 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). 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. 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. 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.
Highlights
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
The Notch signaling pathway positively regulated the process of PDLSC differentiation into Schwann cells (SCs), and the activation of this signaling was important in maintaining the differentiation of PDLSCs to SCs, and SC myelination
We found that periodontal ligament stem cells (PDLSCs) isolated from beagle dogs effectively differentiated into SCs with exposure to a combination of dimethyl sulfoxide (DMSO), basic fibroblast growth factor, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and forskolin.[6,7]
Summary
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. The Schwann cells (SCs) are a glial nerve cell type that form an important part of the Ruffini body of periodontal nerve endings, and play an important role in growth, development and regeneration of peripheral nerves.[1,2] Schwann cells are essential in increasing the density of peripheral nerve endings, and in the improvement of osseoperception. They respond rapidly to nerve injury, and promote axon regrowth and nerve regeneration. We found that periodontal ligament stem cells (PDLSCs) isolated from beagle dogs effectively differentiated into SCs with exposure to a combination of dimethyl sulfoxide (DMSO), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and forskolin.[6,7] Multiple signaling pathways, transcription factors, and neurotrophic factors had been implicated in their differentiation.[3,8] the mechanisms underlying the process of PDLSC differentiation to SCs are poorly characterized
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