Skip to main content

Advertisement

SpringerLink
Log in

Minimal Amelogenin Domain for Enamel Formation

  • Multiscale Experiments and Modeling in Biomaterials and Biological Materials
  • Published:
JOM Aims and scope Submit manuscript

Abstract

Amelogenin is the most abundant matrix protein guiding hydroxyapatite formation in enamel, the durable bioceramic tissue that covers vertebrate teeth. Here, we sought to refine structure-function for an amelogenin domain based on in vitro data showing that a 42-amino acid amelogenin-derived peptide (ADP7) mimicked the formation of hydroxyapatite similar to that observed for the full-length mouse 180-amino acid protein. In mice, we used CRISPR-Cas9 to express only ADP7 by the native amelogenin promoter. Analysis revealed ADP7 messenger RNA expression in developing mouse teeth with the formation of a thin layer of enamel. In vivo, ADP7 peptide partially replaced the function of the full-length amelogenin protein and its several protein isoforms. Protein structure–function relationships identified through in vitro assays can be deployed in whole model animals using CRISPR-Cas9 to validate the function of a minimal protein domain to be translated for clinical use as an enamel biomimetic.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

taken from the mineral maturation zone (Fig. 2). Wt wild-type; ADP7/ADP7 homozygous ADP7 knock-in; DEJ dentine-enamel junction.

Similar content being viewed by others

References

  1. H. Fong, S.N. White, M.L. Paine, W. Luo, M.L. Snead, and M. Sarikaya, J. Bone Miner. Res. 18, 11. (2003).

    Article  Google Scholar 

  2. S.N. White, W. Luo, M.L. Paine, H. Fong, M. Sarikaya, and M.L. Snead, J. Dent. Res. 80, 1. (2001).

    Article  Google Scholar 

  3. M.L. Paine, D.H. Zhu, W. Luo, P. Bringas Jr., M. Goldberg, S.N. White, Y.P. Lei, M. Sarikaya, H.K. Fong, and M.L. Snead, J. Struct. Biol. 132, 3. (2000).

    Article  Google Scholar 

  4. V. Uskokovic, W. Li, and S. Habelitz, J. Bionic. Eng. 8, 2. https://doi.org/10.1016/S1672-6529(11)60017-6 (2011).

    Article  Google Scholar 

  5. M.L. Snead, D.H. Zhu, Y. Lei, W. Luo, P.O. Bringas Jr., H.M. Sucov, R.J. Rauth, M.L. Paine, and S.N. White, Biomaterials 32, 12. https://doi.org/10.1016/j.biomaterials.2011.01.024 (2011).

    Article  Google Scholar 

  6. S. Bechtle, S. Habelitz, A. Klocke, T. Fett, and G.A. Schneider, Biomaterials 31, 2. https://doi.org/10.1016/j.biomaterials.2009.09.050 (2010).

    Article  Google Scholar 

  7. S.N. White, M.L. Paine, A.Y. Ngan, V.G. Miklus, W. Luo, H. Wang, and M.L. Snead, J. Biol. Chem. 282, 8. (2007).

    Article  Google Scholar 

  8. M.L. Snead, D.H. Zhu, Y.P. Lei, S.N. White, C.M. Snead, W. Luo, and M.L. Paine, Mater. Sci. Eng. C 26, 8. https://doi.org/10.1016/J.Msec.2005.08.030 (2006).

    Article  Google Scholar 

  9. S.N. White, V.G. Miklus, P.P. Chang, A.A. Caputo, H. Fong, M. Sarikaya, W. Luo, M.L. Paine, and M.L. Snead, J. Prosthet. Dent. 94, 4. (2005).

    Article  Google Scholar 

  10. M.L. Paine, S.N. White, W. Luo, H. Fong, M. Sarikaya, and M.L. Snead, Matrix Biol. 20, 5–6. (2001).

    Article  Google Scholar 

  11. M.L. Snead, M.L. Paine, W. Luo, D.H. Zhu, B. Yoshida, Y.P. Lei, C.T. Paine, L.S. Chen, J.M. Burstein, S. Jitpukdeebudintra, S.N. White, and P. Bringas Jr., Connect. Tissue Res. 38, 1–4. (1998).

    Article  Google Scholar 

  12. I. Johansson, E. Witkowska, B. Kaveh, P. Lif Holgerson and A.C. Tanner, J. Dent. Res., 95, 1 (2016) https://doi.org/10.1177/0022034515609554.

  13. M.A. Taubman, and D.A. Nash, Nat. Rev. Immunol. 6, 7. (2006).

    Article  Google Scholar 

  14. P.W. Caufield, Y.Li and A. Dasanayake, Compend. Contin. Educ. Dent., 26, 5 Suppl 1 (2005).

  15. C.F. Shuler, J. Dent. Educ. 65, 10. (2001).

    Article  Google Scholar 

  16. C. Robinson, R.C. Shore, S.J. Brookes, S. Strafford, S.R. Wood, and J. Kirkham, Crit. Rev. Oral. Biol. Med. 11, 4. (2000).

    Article  Google Scholar 

  17. N.J. Kassebaum, E. Bernabe, M. Dahiya, B. Bhandari, C.J. Murray, and W. Marcenes, J. Dent. Res. 94, 5. https://doi.org/10.1177/0022034515573272 (2015).

    Article  Google Scholar 

  18. R.S. Lacruz, S. Habelitz, J.T. Wright, and M.L. Paine, Physiol. Rev. 97, 3. https://doi.org/10.1152/physrev.00030.2016 (2017).

    Article  Google Scholar 

  19. JAMA, 283, 10 (2000).

  20. USDHHS, Oral Health in America: A report of the Surgeon General, US Department of Health and Human Services, (2000).

  21. M. Pandya, and T.G.H. Diekwisch, Int. J. Oral Sci. 11, 1. https://doi.org/10.1038/s41368-018-0038-6 (2019).

    Article  Google Scholar 

  22. Z. Huang, C.J. Newcomb, Y. Zhou, Y.P. Lei, P. Bringas Jr., S.I. Stupp, and M.L. Snead, Biomaterials 34, 13. https://doi.org/10.1016/j.biomaterials.2013.01.054 (2013).

    Article  Google Scholar 

  23. C.J. Newcomb, R. Bitton, Y.S. Velichko, M.L. Snead, and S.I. Stupp, Small 8, 14. https://doi.org/10.1002/smll.201102150 (2012).

    Article  Google Scholar 

  24. M.L. Snead, Z. Huang, C.J. Newcomb, M.L. Paine, S.N. White, Y. Xu, Y. Zhou, R.S. Lacruz, and S.I. Stupp, Cell to matrix interactions suggest a pathway for enamel regeneration using artificial matrices, M (Bentham, Goldberg (Saif Zone, Sharjah, UAE, 2010), pp 201–225.

    Google Scholar 

  25. Z. Huang, C.J. Newcomb, P. Bringas Jr., S.I. Stupp, and M.L. Snead, Biomaterials 31, 35. https://doi.org/10.1016/j.biomaterials.2010.08.013 (2010).

    Article  Google Scholar 

  26. Z. Huang, T.D. Sargeant, J.F. Hulvat, A. Mata, P. Bringas Jr., C.Y. Koh, S.I. Stupp, and M.L. Snead, J. Bone Miner. Res. 23, 12. https://doi.org/10.1359/jbmr.080705 (2008).

    Article  Google Scholar 

  27. D.T. Yucesoy, H. Fong, C. Gresswell, S. Saadat, W.O. Chung, S. Dogan, and M. Sarikaya, J. Dent. Res. 97, 13. https://doi.org/10.1177/0022034518789898 (2018).

    Article  Google Scholar 

  28. S. Kim, M. Katchooi, B. Bayiri, M. Sarikaya, A.M. Korpak, and G.J. Huang, Am. J. Orthod. Dentofacial Orthop. 149, 5. https://doi.org/10.1016/j.ajodo.2015.10.025 (2016).

    Article  Google Scholar 

  29. Q. Ruan, Y. Zhang, X. Yang, S. Nutt, and J. Moradian-Oldak, Acta Biomater. 9, 7. https://doi.org/10.1016/j.actbio.2013.04.004 (2013).

    Article  Google Scholar 

  30. Y. Fan, Z. Sun, and J. Moradian-Oldak, Biomaterials 30, 4. (2009).

    Google Scholar 

  31. L. Wang, X. Guan, C. Du, J. Moradian-Oldak and G.H. Nancollas, J. Phys. Chem. C., 111 (2007).

  32. M. Gungormus, E.E. Oren, J.A. Horst, H. Fong, M. Hnilova, M.J. Somerman, M.L. Snead, R. Samudrala, C. Tamerler, and M. Sarikaya, Int. J. Oral Sci. 4, 2. https://doi.org/10.1038/ijos.2012.40 (2012).

    Article  Google Scholar 

  33. D. Zhu, M.L. Paine, W. Luo, P. Bringas Jr., and M.L. Snead, J. Biol. Chem. 281, 30. (2006).

    Article  Google Scholar 

  34. M.L. Paine, W. Luo, D.H. Zhu, P. Bringas Jr., and M.L. Snead, J. Bone Miner. Res. 18, 3. (2003).

    Article  Google Scholar 

  35. Y. Xu, Y.L. Zhou, F.J. Gonzalez, and M.L. Snead, J. Biol. Chem. 282, 41. (2007).

    Google Scholar 

  36. Y. Xu, Y.L. Zhou, R.L. Erickson, O.A. Macdougald, and M.L. Snead, Biochem. Biophys. Res. Commun. 354, 1. (2007).

    Article  Google Scholar 

  37. M.L. Snead, M.L. Paine, L.S. Chen, B.Y. Luo, D.H. Zhou, Y.P. Lei, Y.H. Liu, and R.E. Maxson Jr., Connect. Tissue Res. 35, 1–4. (1996).

    Article  Google Scholar 

  38. S. Geng, S.N. White, M.L. Paine and M.L. Snead, J. Biol. Chem., (2015).

  39. E.M. Southern, J. Mol. Biol. 98, 3. https://doi.org/10.1016/s0022-2836(75)80083-0 (1975).

    Article  Google Scholar 

  40. Y.L. Zhou, Y. Lei, and M.L. Snead, J. Biol. Chem. 275, 37. (2000).

    Google Scholar 

  41. S. Risnes, Scanning Microsc. 1, 4. (1987).

    Google Scholar 

  42. P.H. Krebsbach, S.K. Lee, Y. Matsuki, C.A. Kozak, K.M. Yamada, and Y. Yamada, J. Biol. Chem. 271, 8. (1996).

    Google Scholar 

  43. S.R. Stock, A.E. Vieira, A.C. Delbem, M.L. Cannon, X. Xiao, and F.D. Carlo, J. Struct. Biol. 161, 2. (2008).

    Google Scholar 

  44. M.L. Paine, W. Luo, H.J. Wang, P. Bringas Jr., A.Y. Ngan, V.G. Miklus, D.H. Zhu, M. MacDougall, S.N. White, and M.L. Snead, J. Biol. Chem. 280, 36. https://doi.org/10.1074/jbc.M502991200 (2005).

    Article  Google Scholar 

  45. J.A. Doudna, and E. Charpentier, Science 346, 6213. https://doi.org/10.1126/science.1258096 (2014).

    Article  Google Scholar 

  46. E. Charpentier and L.A. Marraffini, Curr. Opin. Microbiol., 19 (2014) https://doi.org/10.1016/j.mib.2014.07.001.

  47. P. Yang, S.J. Chou, J. Li, W. Hui, W. Liu, N. Sun, R.Y. Zhang, Y. Zhu, M.L. Tsai, H.I. Lai, M. Smalley, X. Zhang, J. Chen, Z. Romero, D. Liu, Z. Ke, C. Zou, C.F. Lee, S.J. Jonas, Q. Ban, P.S. Weiss, D.B. Kohn, K. Chen, S.H. Chiou, and H.R. Tseng, Sci. Adv. 6, 43. https://doi.org/10.1126/sciadv.abb7107 (2020).

    Article  Google Scholar 

  48. H. Frangoul, D. Altshuler, M.D. Cappellini, Y.S. Chen, J. Domm, B.K. Eustace, J. Foell, J. de la Fuente, S. Grupp, R. Handgretinger, T.W. Ho, A. Kattamis, A. Kernytsky, J. Lekstrom-Himes, A.M. Li, F. Locatelli, M.Y. Mapara, M. de Montalembert, D. Rondelli, A. Sharma, S. Sheth, S. Soni, M.H. Steinberg, D. Wall, A. Yen, S. Corbacioglu, and N. Engl, J. Med. https://doi.org/10.1056/NEJMoa2031054 (2020).

    Article  Google Scholar 

  49. M. Gungormus, M. Branco, H. Fong, J.P. Schneider, C. Tamerler, and M. Sarikaya, Biomaterials 31, 28. https://doi.org/10.1016/j.biomaterials.2010.06.010 (2010).

    Article  Google Scholar 

  50. M.L. Snead, Connect. Tissue Res., 44 Suppl 1 (2003).

  51. M.L. Paine, and M.L. Snead, J. Bone Miner. Res. 12, 2. (1997).

    Article  Google Scholar 

  52. K.M. Bromley, R. Lakshminarayanan, Y.P. Lei, M.L. Snead, and J. Moradian-Oldak, Cells Tissues Organs 194, 2–4. https://doi.org/10.1159/000324342 (2011).

    Article  Google Scholar 

  53. R. Lakshminarayanan, K.M. Bromley, Y.P. Lei, M.L. Snead, and J. Moradian-Oldak, J. Biol. Chem. 285, 52. https://doi.org/10.1074/jbc.M110.131136 (2010).

    Article  Google Scholar 

  54. M.L. Paine, H.J. Wang, W. Luo, P.H. Krebsbach, and M.L. Snead, J. Biol. Chem. 278, 21. (2003).

    Google Scholar 

  55. M.L. Paine, Y.P. Lei, K. Dickerson, and M.L. Snead, J. Biol. Chem. 277, 19. (2002).

    Article  Google Scholar 

  56. J. Moradian-Oldak, M.L. Paine, Y.P. Lei, A.G. Fincham, and M.L. Snead, J. Struct. Biol. 131, 1. (2000).

    Article  Google Scholar 

  57. Y. Bai, Z. Yu, L. Ackerman, Y. Zhang, J. Bonde, W. Li, Y. Cheng and S. Habelitz, Proc. Natl. Acad. Sci. U S A, 117, 32 (2020) https://doi.org/10.1073/pnas.2007838117.

  58. P.A. Fang, H.C. Margolis, J.F. Conway, J.P. Simmer, G.H. Dickinson, and E. Beniash, Cells Tissues Organs 194, 2–4. https://doi.org/10.1159/000324250 (2011).

    Article  Google Scholar 

  59. P.A. Fang, J.F. Conway, H.C. Margolis, J.P. Simmer and E. Beniash, Proc. Natl. Acad. Sci. U S A, 108, 34 (2011) https://doi.org/10.1073/pnas.1106228108.

  60. K.M. Bromley, A.S. Kiss, S.B. Lokappa, R. Lakshminarayanan, D. Fan, M. Ndao, J.S. Evans, and J. Moradian-Oldak, J. Biol. Chem. 286, 40. https://doi.org/10.1074/jbc.M111.250928 (2011).

    Article  Google Scholar 

  61. C. Robinson, R.C. Shore, S.R. Wood, S.J. Brookes, D.A. Smith, J.T. Wright, S. Connell and J. Kirkham, Connect. Tissue Res., 44 Suppl 1 (2003).

  62. V. Imbeni, J.J. Kruzic, G.W. Marshall, S.J. Marshall, and R.O. Ritchie, Nat. Mater. 4, 3. (2005).

    Article  Google Scholar 

  63. S. Habelitz, J. Dent. Res. 94, 6. https://doi.org/10.1177/0022034515577963 (2015).

    Article  Google Scholar 

  64. M.L. Snead, M. Zeichner-David, T. Chandra, K.J. Robson, S.L. Woo and H.C. Slavkin, Proc. Natl. Acad. Sci. U S A, 80, 23 (1983).

  65. J.D. Bartlett, B. Ganss, M. Goldberg, J. Moradian-Oldak, M.L. Paine, M.L. Snead, X. Wen, S.N. White and Y.L. Zhou, Curr. Top. Dev. Biol., 74 (2006).

  66. J.P. Simmer, C.C. Hu, E.C. Lau, P. Sarte, H.C. Slavkin, and A.G. Fincham, Calcif. Tissue Int. 55, 4. (1994).

    Article  Google Scholar 

  67. E.C. Lau, J.P. Simmer, P. Bringas Jr., D.D. Hsu, C.C. Hu, M. Zeichner-David, F. Thiemann, M.L. Snead, H.C. Slavkin, and A.G. Fincham, Biochem. Biophys. Res. Commun. 188, 3. (1992).

    Article  Google Scholar 

  68. L.B. Martin, A. Boyde, and F.E. Grine, Scanning Microsc. 2, 3. (1988).

    Google Scholar 

  69. E. Beniash, R.A. Metzler, R.S.K. Lam, and P.U.P.A. Gilbert, J. Struct. Biol. 166, 2. https://doi.org/10.1016/j.jsb.2009.02.001 (2009).

    Article  Google Scholar 

  70. E. Beniash, J.P. Simmer, and H.C. Margolis, J. Struct. Biol. 149, 2. (2005).

    Article  Google Scholar 

Download references

Acknowledgements

Discussions with colleagues were instructive and appreciated. The comments of the three anonymous reviewers served to improve the manuscript and we are grateful for their guidance.

Author information

Authors and Affiliations

  1. Herman Ostrow School of Dentistry of USC, Center for Craniofacial Molecular Biology, The University of Southern California, Los Angeles, CA, 90033, USA

    Shuhui Geng, Yaping Lei & Malcolm L. Snead

  2. School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China

    Shuhui Geng

  3. Biology and Biologic Engineering, California Institute of Technology, Pasadena, CA, 91125, USA

    Yaping Lei

Authors
  1. Shuhui Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yaping Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Malcolm L. Snead
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Malcolm L. Snead.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 17006 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Geng, S., Lei, Y. & Snead, M.L. Minimal Amelogenin Domain for Enamel Formation. JOM 73, 1696–1704 (2021). https://doi.org/10.1007/s11837-021-04687-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11837-021-04687-x

Search

Navigation