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Induction of dental pulp stem cell differentiation into odontoblasts by electroporation-mediated gene delivery of growth/differentiation factor 11 (Gdf11)

Gene Therapy volume 9, pages 814–818 (2002)Cite this article

Abstract

The long-term goal of dental treatment is to preserve teeth and prolong their function. In dental caries an efficient method is to cap the exposed dental pulp and conserve the pulp tissue with reparative dentin. We examined whether growth/differentiation factor 11 (GDF11), a morphogen could enhance the healing potential of pulp tissue to induce differentiation of pulp stem cells into odontoblasts by electroporation-mediated gene delivery. Recombinant human GDF11 induced the expression of dentin sialoprotein (Dsp), a differentiation marker for odontoblasts, in mouse dental papilla mesenchyme in organ culture. The Gdf11 cDNA plasmid which was transferred into mesenchymal cells derived from mouse dental papilla by electroporation, induced the expression of Dsp. The in vivo transfer of Gdf11 by electroporation stimulated the reparative dentin formation during pulpal wound healing in canine teeth. These results provide the scientific basis and rationale for gene therapy for endodontic treatments in oral medicine and dentistry.

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References

  1. Reddi AH . Role of morphogenetic proteins in skeletal tissue engineering and regeneration Nature Biotech 1998 16: 247–252

    Article  CAS  Google Scholar 

  2. Kirker-Head CA . Potential applications and deliver strategies for bone morphogenetic proteins Adv Drug Del Rev 2000 43: 65–92

    Article  CAS  Google Scholar 

  3. Nakashima M . The induction of reparative dentine in the amputated dental pulp of the dog by bone morphogenetic protein Archs Oral Biol 1990 35: 493–497

    Article  CAS  Google Scholar 

  4. Nakashima M . Induction of dentin formation on canine amputated pulp by recombinant human bone morphogenetic protein (BMP)-2 and -4 J Dent Res 1994 73: 1515–1522

    Article  CAS  Google Scholar 

  5. Nakashima M . Induction of dentine in amputated pulp of the dogs by recombinant human bone morphogenetic proteins-2 and -4 with collagen matrix Archs Oral Biol 1994 39: 1085–1089

    Article  CAS  Google Scholar 

  6. Rutherford RB et al. Induction of reparative dentin formation in monkeys by recombinant human osteogenic protein-1 Arch Oral Biol 1993 38: 571–576

    Article  CAS  Google Scholar 

  7. Rutherford RB et al. Time course of the induction of reparative dentin formation in monkeys by recombinant human osteogenic protein-1 Arch Oral Biol 1994 39: 833–838

    Article  CAS  Google Scholar 

  8. Rutherford RB, Spangberg L, Tucker M, Charette M . Transdentinal stimulation of reparative dentine formation by osteogenic protein-1 in monkeys Arch Oral Biol 1995 40: 681–683

    Article  CAS  Google Scholar 

  9. Winn SR, Hu Y, Sfeir C, Hollinger JO . Gene therapy approaches for modulating bone regeneration Adv Drug Del Rev 2000 42: 121–138

    Article  CAS  Google Scholar 

  10. McPherron AC, Lawler AM, Lee SJ . Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11 Nature Genet 1999 22: 260–264

    Article  CAS  Google Scholar 

  11. Nakashima M, Toyono T, Akamine A, Joyner A . Expression of growth/differentiation factor 11, a new member of the BMP/TGFβ superfamily during mouse embryogenesis Mech Dev 1999 80: 185–189

    Article  CAS  Google Scholar 

  12. Gamer LW et al. A novel BMP expressed in developing mouse limb, spinal cord, and tail bud is a potent mesoderm inducer in Xenopus embryos Dev Biol 1999 208: 222–232

    Article  CAS  Google Scholar 

  13. Crystal RG . Transfer of genes to humans: early lessons and obstacles to success Science 1995 270: 404–410

    Article  CAS  Google Scholar 

  14. Neumann EM, Schaefer-Ridder YW, Hofschneider PH . Gene transfer into mouse lyoma cells by electroporation in high electric fields EMBO J 1982 1: 841–845

    Article  CAS  Google Scholar 

  15. Fromm M, Taylor LP, Walbot V . Expression of genes transferred into monocot and dicot plant cells by electroporation Proc Natl Acad Sci USA 1985 82: 5824–5828

    Article  CAS  Google Scholar 

  16. Andreason GL, Evans GA . Introduction and expression of DNA molecules in eukaryotic cells by electroporation Biotechniques 1988 6: 650–660

    CAS  PubMed  Google Scholar 

  17. Chowrira GM, Akella V, Fuerst PE, Lurquin PF . Transgenic grain legumes obtained by in planta electroporation-mediated gene transfer Mol Biotechnol 1996 5: 85–96

    Article  CAS  Google Scholar 

  18. Muramatsu T, Nakamura A, Park HM . In vivo electroporation: a powerful and convenient means of nonviral gene transfer to tissues of living animals Int J Mol Med 1998 1: 55–62

    CAS  Google Scholar 

  19. Weaver JC . Electroporation: a general phenomenon for manipurating cells and tissues J Cell Biochem 1993 51: 426–435

    Article  CAS  Google Scholar 

  20. Hofmann GA . Instrumentation Nickoloff JA (eds); Methods in Molecular Biology. Electroporation Protocols for Microorganisms Humana Press 1995 pp 27–45

  21. Dev SB, Hofmann GA . Electrochemotherapy – a novel method of cancer treatment Cancer Treat Rev 1994 20: 105–115

    Article  CAS  Google Scholar 

  22. Nakashima M, Nagasawa H, Yamada Y, Reddi AH . Regulatory role of transforming growth factor-β, bone morphogenetic protein-2, and protein-4 on gene expression of extracellular matrix proteins and differentiation of dental pulp cells Dev Biol 1994 162: 18–28

    Article  CAS  Google Scholar 

  23. Yokose S et al. Establishment and characterization of a culture system for enzymatically released rat dental pulp cells Calcif Tissue Int 2000 66: 139–144

    Article  CAS  Google Scholar 

  24. Couble ML et al. Odontoblast differentiation of human dental pulp cells in explant cultures Calcif Tissue Int 2000 66: 129–138

    Article  CAS  Google Scholar 

  25. D'Souza RN et al. Gene expression patterns of murine dentin matrix protein 1 (Dmp1) and dentin sialophosphoprotein (DSPP) suggest distinct developmental functions in vivo J Bone Min Res 1997 12: 2040–2049

    Article  CAS  Google Scholar 

  26. Avery JK . Dentin Bhaskar SN (eds); Orban's Oral Histology and Embryology Mosby 1980 pp 107–140

  27. Baume LJ . Dental pulp conditions in relation to carious lesions Int Dent J 1970 20: 309–337

    CAS  PubMed  Google Scholar 

  28. Takuma S, Yanagisawa T, Lin WL . Ultrastructural and microanalytical aspects of developing osteodentin in rat incisors Calcif Tissue Res 1977 24: 215–222

    Article  CAS  Google Scholar 

  29. Tziafas D, Smith AJ, Lesot H . Designing new treatment strategies in vital pulp therapy J Dent 2000 28: 77–92

    Article  CAS  Google Scholar 

  30. Newman CM, Lawrie A, Brisken AF . Cumberland DC. Ultrasound gene therapy: on the road from concept to reality Echocardiography 2001 18: 339–347

    Article  CAS  Google Scholar 

  31. Nakashima M . Establishment of primary cultures of pulp cells from bovine permanent incisors Archs Oral Biol 1991 36: 655–663

    Article  CAS  Google Scholar 

  32. Gu K et al. Molecular cloning of a human dentin sialophosphoprotein gene Eur J Oral Sci 2000 108: 35–42

    Article  CAS  Google Scholar 

  33. Kiefer MC, Saphire AC, Bauer DM, Barr PJ . The cDNA and derived amino acid sequences of human and bovine bone Gla protein Nucleic Acids Res 1990 18: 1909

    Article  CAS  Google Scholar 

  34. Alonso S, Minty A, Bourlet Y, Buckingham M . Comparison of three actin-coding sequences in the mouse; evolutionary relationships between the actin genes of warm-blooded vertebrates J Mol Evol 1986 23: 11–22

    Article  CAS  Google Scholar 

  35. Platt KA, Michaud J, Joyner AL . Expression of the mouse Gli and Ptc genes is adjacent to embryonic sources of hedgehog signals a conservation of pathways between flies and mice Mech Dev 1997 62: 121–135

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to K Hirakawa and T Yamauchi of Tokiwa Science for their help and to Genetic Institutes for their kind gift of recombinant human GDF11. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan, No. 11470406.

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Authors and Affiliations

  1. Department of Clinical Oral Molecular Biology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

    M Nakashima, K Mizunuma & A Akamine

  2. Department of Orthodontics, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

    T Murakami

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  1. M Nakashima
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  2. K Mizunuma
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  3. T Murakami
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  4. A Akamine
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Nakashima, M., Mizunuma, K., Murakami, T. et al. Induction of dental pulp stem cell differentiation into odontoblasts by electroporation-mediated gene delivery of growth/differentiation factor 11 (Gdf11). Gene Ther 9, 814–818 (2002). https://doi.org/10.1038/sj.gt.3301692

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