Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

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doi: 10.17219/acem/131219

Publication type: original article

Language: English

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Notch pathway activation promotes the differentiation of beagle dog periodontal ligament stem cells to Schwann cells

Xiaojie Li1,A,B,C,D,E,F, Dapeng Liao2,A,B,C,D,E,F, Gang Sun2,B,C,E,F, Hanwen Chu2,B,C,E,F

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.

Key words

differentiation, Schwann cells, periodontal ligament stem cells, Notch signaling pathway

References (17)

  1. Mirsky R, Jessen KR. Schwann cell development, differentiation and myelination. Curr Opin Neurobiol. 1996;6(1):89–96. doi:10.1016/s0959-4388(96)80013-4
  2. Frostick SP, Yin Q, Kemp GJ. Schwann cells, neurotrophic factors, and peripheral nerve regeneration. Microsurgery. 1998;18(7):397–405. doi:10.1002/(sici)1098-2752(1998)18:7<397::aid-micr2>;2-f
  3. Jessen KR, Mirsky R. The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci. 2005;6(9):671–682. doi:10.1038/nrn1746
  4. Hammarberg H, Risling M, Hokfelt T, Cullheim S, Piehl F. Expression of insulin-like growth factors and corresponding binding proteins (IGFBP 1-6) in rat spinal cord and peripheral nerve after axonal injuries. J Comp Neurol. 1998;400(1):57–72. PMID:9762866
  5. Mosahebi A, Woodward B, Wiberg M, Martin R, Terenghi G. Retroviral labeling of Schwann cells: In vitro characterization and in vivo transplantation to improve peripheral nerve regeneration. Glia. 2001;34(1):8–17. doi:10.1002/glia.1035
  6. Li X, Gong P, Liao D. In vitro neural/glial differentiation potential of periodontal ligament stem cells. Arch Med Sci. 2010;6(5):678–685. doi:10.5114/aoms.2010.17080
  7. Li X, Liao D, Gong P, Dong Y, Sun G. Biological behavior of neurally differentiated periodontal ligament stem cells on different titanium implant surfaces. J Biomed Mater Res A. 2014;102(8):2805–2812. doi:10.1002/jbm.a.34953
  8. Ijuin K, Nakanishi K, Ito K. Different downstream pathways for Notch signaling are required for gliogenic and chondrogenic specification of mouse mesencephalic neural crest cells. Mech Dev. 2008;125(5–6):462–474. doi:10.1016/j.mod.2008.01.008
  9. Dapeng L, Xiaojie L, Ping G, Yan D, Gang S. Erk1/2 signalling is involved in the differentiation of periodontal ligament stem cells to Schwann cells in dog. Arch Oral Biol. 2014;59(5):487–491. doi:10.1016/j.archoralbio.2014.02.010
  10. Joseph NM, Mukouyama YS, Mosher JT, et al. Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells. Development. 2004;131(22):5599–5612. doi:10.1242/dev.01429
  11. Shi Y, Shao Q, Li Z, et al. Myt1L promotes differentiation of oligodendrocyte precursor cells and is necessary for remyelination after lysolecithin-induced demyelination. Neurosci Bull. 2018;34(2):247–260. doi:10.1007/s12264-018-0207-9
  12. Woodhoo A, Alonso MB, Droggiti A, et al. Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity. Nat Neurosci. 2009;12(7):839–847. doi:10.1038/nn.2323
  13. Wu LM, Wang J, Conidi A, et al. Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination. Nat Neurosci. 2016;19(8):1060–1072. doi:10.1038/nn.4322
  14. Fiuza UM, Arias AM. Cell and molecular biology of Notch. J Endocrinol. 2007;194(3):459–474. doi:10.1677/JOE-07-0242
  15. Seo BM, Miura M, Gronthos S, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet. 2004;364(9429):149–155. doi:10.1016/S0140-6736(04)16627-0
  16. Vasquez-Del Carpio R, Kaplan FM, Weaver KL, et al. Assembly of a Notch transcriptional activation complex requires multimerization. Mol Cell Biol. 2011;31(7):1396–1408. doi:10.1128/MCB.00360-10
  17. Kingham PJ, Mantovani C, Terenghi G. Notch independent signalling mediates Schwann cell-like differentiation of adipose derived stem cells. Neurosci Lett. 2009;467(2):164–168. doi:10.1016/j.neulet.2009.10.030