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Dentin matrix protein 1 induces cytodifferentiation of dental pulp stem cells into odontoblasts

Abstract

Odontoblasts are postmitotic cells that differentiate from the dental papilla. These cells are responsible for producing the calcified dentin matrix. The pulp-odontoblast interphase contains undifferentiated mesenchymal stem cells, which have the ability to cytodifferentiate into odontoblast-like cells in response to specific signaling molecules. Dentin matrix protein 1 (DMP1) is one of the dentin noncollagenous extracellular matrix proteins that has been implicated in regulation of mineralization. In this study, we have examined the potential role of DMP1 in inducing cytodifferentiation of dental pulp stem cells into odontoblast-like cells and formation of reparative dentin in a rat model. Cavities were drilled and pulps exposed in maxillary first molars. Collagen matrix impregnated with recombinant DMP1 was implanted directly in Group 1, while calcium hydroxide, a commonly used pulp-capping agent was implanted in group 2, collagen matrix that was not impregnated with rDMP1 was implanted directly in group 3, which served as control. Each of these three groups was subdivided into two subgroups, A for 2 weeks time duration and B for 4 weeks duration. At the end of the time period the maxillae were excised, tissues were processed for histological and immunohistochemical evaluations. The results showed that DMP1 could act as a morphogen on undifferentiated mesenchymal cells present in the dentin–pulp complex. These differentiated cells had the potential to regenerate dentin-like tissue, which was confirmed by the presence of collagenous matrix, odontoblast specific markers and calcified deposits.

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References

  1. Boland GM, Perkins G, Hall DJ, Tuan RS . Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem 2004; 93: 1210–1230.

    Article  CAS  Google Scholar 

  2. Cheng L, Alvares LE, Ahmed MU, El-Hanfy AS, Dietrich S . The epaxial-hypaxial subdivision of the avian somite. Dev Biol 2004; 274: 348–369.

    Article  CAS  Google Scholar 

  3. Hu B, Nadiri A, Bopp-Kuchler S, Perrin-Schmitt F, Wang S, Lesot H . Dental epithelial histo-morphogenesis in the mouse: positional information versus cell history. Arch Oral Biol 2005; 50: 131–136.

    Article  Google Scholar 

  4. Tucker AS, Al Khamis A, Sharpe PT . Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme. Dev Dyn 1998; 212: 533–539.

    Article  CAS  Google Scholar 

  5. Thesleff I . Developmental biology and building a tooth. Quintessence Int 2003; 34: 613–620.

    PubMed  Google Scholar 

  6. Kollar EJ, Lumsden AG . Tooth morphogenesis: the role of the innervation during induction and pattern formation. J Biol Buccale 1979; 7: 49–60.

    CAS  PubMed  Google Scholar 

  7. George A, Sabsay B, Simonian PAL, Veis A . Characterization of a novel dentin matrix acidic Phosphoprotein. J Biol Chem 1993; 268: 12624–12630.

    CAS  PubMed  Google Scholar 

  8. Veis A . Mineral-matrix interactions in bone and dentin. Bone Miner Res 1993; S2: S493–S497.

    Google Scholar 

  9. Gao H, Ji B, Jager IL, Arzt E, Fratzl P . Materials become insensitive to flaws at nanoscale: lessons from nature. Proc Natl Acad Sci USA 2003; 100: 5597–5600.

    Article  CAS  Google Scholar 

  10. Sabsay B, Stetler-Stevenson WG, Lechner JH, Veis A . Domain structure and sequence distribution in dentin phosphophoryn. Biochem J 1991; 276: 699–707.

    Article  CAS  Google Scholar 

  11. Boskey AL . The role of extracellular matrix components in dentin mineralization. Crit Rev Oral Biol Med 1991; 2: 369–387.

    Article  CAS  Google Scholar 

  12. Butler WT . Dentin matrix proteins. Eur J Oral Sci 1998; 106: 204–210.

    Article  CAS  Google Scholar 

  13. George A . Dentin matrix proteins. In: Rabie AM and Urist MR (eds). Bone Formation and Repair. Elsevier; Amsterdam, 1997, pp 125–133.

    Google Scholar 

  14. Hao J, Zou B, Narayanan K, George A . Differential expression patterns of the dentin matrix proteins during mineralized tissue formation. Bone 2004; 34: 921–932.

    Article  CAS  Google Scholar 

  15. Narayanan K, Ramachandran A, Hao J, George A . Differentiation of embryonic mesenchymal cells to odontoblast-like cells by overexpression of dentin matrix protein 1. Proc Natl Acad Sci USA 2001; 98: 4516–4521.

    Article  CAS  Google Scholar 

  16. Linde A . Dentin Matrix Proteins: composition and possible functions in calcification. Anat Rec 1989; 224: 154–166.

    Article  CAS  Google Scholar 

  17. Butler WT, Ritchie H . The nature and functional significance of dentin extracellular matrix proteins. Int J Dev Biol 1995; 39: 169–179.

    CAS  PubMed  Google Scholar 

  18. Ten Cate AR . Dentin/pulp complex reactions: a reaction. Proc Finn Dent Soc 1992; 88: 275–278.

    PubMed  Google Scholar 

  19. Smith AJ . Odontoblast stimulation in ferrets by dentine matrix components. Arch Oral Biol 1994; 39: 13–22.

    Article  CAS  Google Scholar 

  20. Rutherford B, Fitzgerald M . A new biological approach to vital pulp therapy. Crit Rev Oral Biol Med 1995; 6: 218–229.

    Article  CAS  Google Scholar 

  21. Goldberg M, Smith AJ . Cells and extracellular matrices of dentin and pulp: A biological basis for repair and tissue engineering. Crit Rev Oral Biol Med 2004; 15: 13–27.

    Article  Google Scholar 

  22. Smith AJ, Lesot H . Induction and regulation of crown dentinogenesis: embryonic events as a template for dental tissue repair. Crit Rev Oral Biol Med 2001; 12: 425–437.

    Article  CAS  Google Scholar 

  23. Smith AJ, Tobias RS, Cassidy N, Begue-Kirn C, Ruch JV, Lesot H . Influence of substrate nature and immobilization of implanted dentin matrix components during induction of reparative dentinogenesis. Connect Tissue Res 1995; 321: 291–296.

    Article  Google Scholar 

  24. Goldberg M, Takagi M . Dentine proteoglycans: composition, ultrastructure and functions. Histochem J 1993; 11: 781–806.

    Article  Google Scholar 

  25. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S . Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA 2000; 25: 13625–13630.

    Article  Google Scholar 

  26. Murray PE, Hafez AA, Smith AJ, Cox CF . Hierarchy of pulp capping and repair activities responsible for dentin bridge formation. Am J Dent 2002; 4: 236–243.

    Google Scholar 

  27. Ruch JV . Determinisms of odontogenesis. Revis Biol Celular 1987; 14: 1–99.

    CAS  PubMed  Google Scholar 

  28. Lesot H . Collagen type I trimer synthesis by cultured embryonic mouse molars. Eur J Biochem 1981; 3: 541–546.

    Article  Google Scholar 

  29. Veis A, Perry A . The phosphoprotein of the dentin matrix. Biochemistry 1967; 8: 2409–2416.

    Article  Google Scholar 

  30. Maier GD, Evans JS, Veis A . Characterization of the primary gene product of rat incisor alpha phosphophoryn. Biochemistry 1985; 23: 6370–6374.

    Article  Google Scholar 

  31. Goldberg M, Lasfargues JJ . Pulpo-dentinal complex revisited. J Dent 1995; 1: 15–20.

    Article  Google Scholar 

  32. Butler WT, Ritchie H . The nature and functional significance of dentin extracellular matrix proteins. Int J Dev Biol 1995; 39: 169–179.

    CAS  PubMed  Google Scholar 

  33. Pashley DH . Dynamics of the pulpo-dentin complex. Crit Rev Oral Biol Med 1996; 2: 104–133.

    Article  Google Scholar 

  34. Schroder U . Effects of calcium hydroxide-containing pulp-capping agents on pulp cell migration, proliferation, and differentiation. J Dent Res 1985; 64: 541–548.

    Article  Google Scholar 

  35. Cox E, Bergenholtz G, Heys DR, Syed SA, Fitzgerald M, Heys RJ . Pulp capping of dental pulp mechanically exposed to oral microflora: a 1–2 year observation of wound healing in the monkey. J Oral Pathol 1985; 2: 156–168.

    Article  Google Scholar 

  36. Hu CC, Zhang C, Qian Q, Tatum NB . Reparative dentin formation in rat molars after direct pulp capping with growth factors. J Endod 1998; 11: 744–751.

    Article  Google Scholar 

  37. Nakashima M, Mizunuma K, Murakami T, Akamine A . Induction of dental pulp stem cell differentiation into odontoblasts by electroporation-mediated gene delivery of growth/differentiation factor. Gene Therapy 2002; 9: 814–818.

    Article  CAS  Google Scholar 

  38. Srinivasan R, Chen B, Gorski JP, George A . Recombinant expression and characterization of dentin matrix protein 1. Connective Tiss Res 1999; 40: 251–258.

    Article  CAS  Google Scholar 

  39. Harrop TJ, Mackay B . Electron microscopic observations on healing in dental pulp in the rat. Arch Oral Biol 1968; 4: 365–385.

    Article  Google Scholar 

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Acknowledgements

We would like to thank Ms Mei Lin for the help in confocal microsocopy. This study was supported by the NIH Grant to AG (DE11657).

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Correspondence to A George.

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Almushayt, A., Narayanan, K., Zaki, A. et al. Dentin matrix protein 1 induces cytodifferentiation of dental pulp stem cells into odontoblasts. Gene Ther 13, 611–620 (2006). https://doi.org/10.1038/sj.gt.3302687

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