Cell and Tissue Research

, Volume 348, Issue 3, pp 465–473 | Cite as

In-vitro regulation of odontogenic gene expression in human embryonic tooth cells and SHED cells

  • Angelo Leone
  • Ana Angelova Volponi
  • Tara Renton
  • Paul T. Sharpe
Regular Article

Abstract

The bud-to-cap stage transition during early tooth development is a time when the tooth-inducing potential becomes restricted to the mesenchyme. Several key genes, expressed in the mesenchyme at this stage, are an absolute requirement for the progression of tooth development. These include the transcription factors Msx1 and Pax9. The inductive potential of tooth mesenchyme cells is a key requisite for whole-tooth bioengineering and thus identification of cells that can retain this property following expansion in culture is an important as yet unresolved, goal. We show here that in-vitro culture of embryonic human tooth mesenchyme cells and SHED cells express low levels of PAX9 and MSX1 and that these levels can be significantly upregulated by activation of different signalling pathways. Such in-vitro manipulation may thus offer a simple way of maintaining/restoring/inducing the odontogenic-inducing capacity in mesenchymal cells.

Keywords

SHED PAX9 MSX1 Tissue engineering Cell signalling 

References

  1. Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S (2008) Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues. Stem Cells 26(7):1787–1795PubMedCrossRefGoogle Scholar
  2. Arthur A, Shi S, Zannettino AC, Fujii N, Gronthos S, Koblar SA (2009) Implanted adult human dental pulp stem cells induce endogenous axon guidance. Stem Cells 27(9):2229–2237PubMedCrossRefGoogle Scholar
  3. Balic A, Aguila HL, Caimano MJ, Francone VP, Mina M (2010) Characterization of stem and progenitor cells in the dental pulp of erupted and unerupted murine molars. Bone 46(6):1639–1651PubMedCrossRefGoogle Scholar
  4. Baltacioglu E, Tasdemir T, Yuva P, Celik D, Sukuroglu E (2011) Intentional replantation of periodontally hopeless teeth using a combination of enamel matrix derivative and demineralized freeze-dried bone allograft. Int J Periodontics Restorative Dent 31(1):75–81PubMedGoogle Scholar
  5. Bei M, Maas R (1998) FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development. Development 125(21):4325–4333PubMedGoogle Scholar
  6. Cortellini P, Tonetti MS (2011) Clinical and radiographic outcomes of the modified minimally invasive surgical technique with and without regenerative materials: a randomized-controlled trial in intra-bony defects. J Clin Periodontol 38(4):365–373PubMedCrossRefGoogle Scholar
  7. d'Aquino R, Graziano A, Sampaolesi M, Laino G, Pirozzi G, De Rosa A, Papaccio G (2007) Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation. Cell Death Differ 14(6):1162–1171PubMedCrossRefGoogle Scholar
  8. Doble BW, Woodgett JR (2003) GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci 116:1175–1186PubMedCrossRefGoogle Scholar
  9. Duailibi MT, Duailibi SE, Young CS, Bartlett JD, Vacanti JP, Yelick PC (2004) Bioengineered teeth from cultured rat tooth bud cells. J Dent Res 83(7):523–528PubMedCrossRefGoogle Scholar
  10. Fujita T, Yamamoto S, Ota M, Shibukawa Y, Yamada S (2011) Coverage of gingival recession defects using guided tissue regeneration with and without adjunctive enamel matrix derivative in a dog model. Int J Periodontics Restorative Dent 31(3):247–253PubMedGoogle Scholar
  11. Graziano A, d'Aquino R, Laino G, Papaccio G (2008) Dental pulp stem cells: a promising tool for bone regeneration. Stem Cell Rev 4(1):21–26PubMedCrossRefGoogle Scholar
  12. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA 97:13625–13630PubMedCrossRefGoogle Scholar
  13. Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S (2002) Stem cell properties of human dental pulp stem cells. J Dent Res 81(8):531–535PubMedCrossRefGoogle Scholar
  14. Hara K, Yamada Y, Nakamura S, Umemura E, Ito K, Ueda M (2011) Potential characteristics of stem cells from human exfoliated deciduous teeth compared with bone marrow-derived mesenchymal stem cells for mineralized tissue-forming cell biology. J Endod 37(12):1647–1652PubMedCrossRefGoogle Scholar
  15. Hu B, Nadiri A, Bopp-Kuchler S, Perrin-Schmitt F, Wang S, Lesot H (2005) Dental epithelial histo-morphogenesis in the mouse: positional information versus cell history. Arch Oral Biol 50(2):131–136PubMedCrossRefGoogle Scholar
  16. Huang GT, Gronthos S, Shi S (2009) Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 88(9):792–806PubMedCrossRefGoogle Scholar
  17. Ieong CC, Zhou XD, Li JY, Li W, Zhang LL (2011) Possibilities and potential roles of the functional peptides based on enamel matrix proteins in promoting the remineralization of initial enamel caries. Med Hypotheses 76(3):391–394PubMedCrossRefGoogle Scholar
  18. Ikeda E, Morita R, Nakao K, Ishida K, Nakamura T, Takano-Yamamoto T, Ogawa M, Mizuno M, Kasugai S, Tsuji T (2009) Fully functional bioengineered tooth replacement as an organ replacement therapy. Proc Natl Acad Sci USA 106(32):13475–13480PubMedCrossRefGoogle Scholar
  19. Jernvall J, Thesleff I (2000) Reitrative signalling and patterning during mammalian tooth morphogenesis. Mech Dev 92:19–29PubMedCrossRefGoogle Scholar
  20. Jo YY, Lee HJ, Kook SY, Choung HW, Park JY, Chung JH, Choung YH, Kim ES, Yang HC, Choung PH (2007) Isolation and characterization of postnatal stem cells from human dental tissues. Tissue Eng 13(4):767–773PubMedCrossRefGoogle Scholar
  21. Kapferer I, Schmidt S, Gstir R, Durstberger G, Huber LA, Vietor I (2011) Gene-expression profiles of epithelial cells treated with EMD in vitro: analysis using complementary DNA arrays. J Periodontal Res 46(1):118–125PubMedCrossRefGoogle Scholar
  22. Koyama N, Okubo Y, Nakao K, Bessho K (2009) Evaluation of pluripotency in human dental pulp cells. J Oral Maxillofac Surg 67(3):501–506PubMedCrossRefGoogle Scholar
  23. Lesot H, Brook AH (2009) Epithelial histogenesis during tooth development. Arch Oral Biol 54(Suppl 1):S25–S33, ReviewPubMedCrossRefGoogle Scholar
  24. Lumsden AGS (1988) Spatial organization of the epithelium and the role of neural crest cells in the initiation of the mammalian tooth germ. Development 103(Suppl):155–169PubMedGoogle Scholar
  25. Mandler M, Neubüser A (2001) FGF signaling is necessary for the specification of the odontogenic mesenchyme. Dev Biol 240(2):548–559PubMedCrossRefGoogle Scholar
  26. Mina M, Kollar EJ (1987) The induction of odontogenesis in non-dental mesenchyme combined with early murine mandibular arch epithelium. Arch Oral Biol 32:123–127PubMedCrossRefGoogle Scholar
  27. Nakao K, Morita R, Saji Y, Ishida K, Tomita Y, Ogawa M, Saitoh M, Tomooka Y, Tsuji T (2007) The development of a bioengineered organ germ method. Nat Method Mar 4(3):227–230CrossRefGoogle Scholar
  28. Neubüser A, Peters H, Ballings R, Martin GR (1997) Antagonistic interactions between FGF and BMP4 signaling pathways: A mechanism for positioning the sites of tooth formation. Cell 90:147–155CrossRefGoogle Scholar
  29. Ohazama A, Modino SA, Miletich I, Sharpe PT (2004) Stem-cell-based tissue engineering of murine teeth. J Dent Res 83(7):518–522PubMedCrossRefGoogle Scholar
  30. Qu Z, Andrukhov O, Laky M, Ulm C, Matejka M, Dard M, Rausch-Fan X (2011) Effect of enamel matrix derivative on proliferation and differentiation of osteoblast cells grown on the titanium implant surface. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 111(4):517–522PubMedCrossRefGoogle Scholar
  31. Rasperini G, Roccuzzo M, Francetti L, Acunzo R, Consonni D, Silvestri M (2011) Subepithelial connective tissue graft for treatment of gingival recessions with and without enamel matrix derivative: a multicenter, randomized controlled clinical trial. Int J Periodontics Restorative Dent 31(2):133–139PubMedGoogle Scholar
  32. Schröen O, Sahrmann P, Roos M, Attin T, Schmidlin PR (2011) A survey on regenerative surgery performed by Swiss specialists in periodontology with special emphasis on the application of enamel matrix derivatives in infrabony defects. Schweiz Monatsschr Zahnmed 121(2):136–142PubMedGoogle Scholar
  33. Silvestri M, Rasperini G, Milani S (2011) 120 infrabony defects treated with regenerative therapy: long-term results. J Periodontol 82(5):668–675PubMedCrossRefGoogle Scholar
  34. Sugiyama M, Iohara K, Wakita H, Hattori H, Ueda M, Matsushita K, Nakashima M (2011) Dental pulp-derived CD31‾/CD146‾ side population stem/progenitor cells enhance recovery of focal cerebral ischemia in rats. Tissue Eng Part A 17(9–10):1303–1311PubMedCrossRefGoogle Scholar
  35. Thesleff I, Mikkola M (2002) The role of growth factors in tooth development. Int Rev Cytol 217:93–135PubMedCrossRefGoogle Scholar
  36. Thesleff I, Sharpe PT (1997) Signalling networks regulating dental development. Mech Dev 67:111–123PubMedCrossRefGoogle Scholar
  37. Thesleff I, Keränen S, Jernvall J (2001) Enamel knots as signaling centers linking tooth morphogenesis and odontoblast differentiation. Adv Dent Res 15:14–18PubMedCrossRefGoogle Scholar
  38. Tucker A, Sharpe P (2004) The cutting-edge of mammalian development: how the embryo makes teeth. Nat Rev 5:499–508Google Scholar
  39. Tucker AS, Al Khamis A, Sharpe PT (1998) Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme. Dev Dyn 212(4):533–539PubMedCrossRefGoogle Scholar
  40. Volponi AA, Pang Y, Sharpe PT (2010) Stem cell-based biological tooth repair and regeneration. Trends Cell Biol 20(12):715–722PubMedCrossRefGoogle Scholar
  41. Waddington RJ, Youde SJ, Lee CP, Sloan AJ (2009) Isolation of distinct progenitor stem cell populations from dental pulp. Cells Tissues Organs 189(1–4):268–274PubMedCrossRefGoogle Scholar
  42. Wang XJ, Huang H, Yang F, Xia LG, Zhang WJ, Jiang XQ, Zhang FQ (2011) Ectopic study of tissue-engineered bone complex with enamel matrix proteins, bone marrow stromal cells in porous calcium phosphate cement scaffolds, in nude mice. Cell Prolif 44(3):274–282PubMedCrossRefGoogle Scholar
  43. Yalvac ME, Rizvanov AA, Kilic E, Sahin F, Mukhamedyarov MA, Islamov RR, Palotás A (2009) Potential role of dental stem cells in the cellular therapy of cerebral ischemia. Curr Pharm Des 15(33):3908–3916PubMedCrossRefGoogle Scholar
  44. Yamamoto H, Kim EJ, Cho SW, Jung HS (2003) Analysis of tooth formation by reaggregated dental mesenchyme from mouse embryo. J Electron Microsc (Tokyo) 52(6):559–566CrossRefGoogle Scholar
  45. Zhang YD, Chen Z, Song YQ, Liu C, Chen YP (2005) Making a tooth: growth factors, transcription factors and stem cells. Cell Res 15:301–316PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Angelo Leone
    • 2
  • Ana Angelova Volponi
    • 1
  • Tara Renton
    • 3
  • Paul T. Sharpe
    • 1
  1. 1.Department of Craniofacial Development and Stem Cell BiologyDental Institute, Kings College LondonLondonUK
  2. 2.BioNec, Section of Histology and EmbryologyFaculty of Medicine, University of PalermoPalermoItaly
  3. 3.Department of Oral SurgeryDental Institute, King’s College University of LondonLondonUK

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