Abstract
In this chapter the basic premises, the recent findings and the future challenges in the use of amelogenin for enamel tissue engineering are being discoursed on. Results emerging from the experiments performed to assess the fundamental physicochemical mechanisms of the interaction of amelogenin, the main protein of the enamel matrix, and the growing crystals of apatite, are mentioned, alongside a moderately comprehensive literature review of the subject at hand. The clinical importance of understanding this protein/mineral interaction at the nanoscale are highlighted as well as the potential for tooth enamel to act as an excellent model system for studying some of the essential aspects of biomineralization processes in general. The dominant paradigm stating that amelogenin directs the uniaxial growth of apatite crystals in enamel by slowing down the growth of (hk0) faces on which it adheres is being questioned based on the results demonstrating the ability of amelogenin to promote the nucleation and crystal growth of apatite under constant titration conditions designed to mimic those present in the developing enamel matrix. The role of numerous minor components of the enamel matrix is being highlighted as essential and impossible to compensate for by utilizing its more abundant ingredients only. It is concluded that the three major aspects of amelogenesis outlined hereby – (1) the assembly of amelogenin and other enamel matrix proteins, (2) the proteolytic activity, and (3) crystallization – need to be in precise synergy with each other in order for the grounds for the proper imitation of amelogenesis in the lab to be created.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aichmayer B, Wiedemann-Bidlack FB, Gilow C, Simmer JP, Yamakoshi Y, Emmerling F, Margolis HC, Fratzl P (2010) Amelogenin nanoparticles in suspension: deviations from spherical shape and pH-dependent aggregation. Biomacromolecules 11(2):369–376
Aizawa M, Porter AE, Best SM, Bonfield W (2005) Ultrastructural observation of single-crystal apatite fibres. Biomaterials 26:3427–3433
Aldaye FA, Palmer AL, Sleiman HF (2008) Assembling materials with DNA as the guide. Science 321:1795–1799
Aoba T, Fukae M, Tanabe T, Shimizu M, Moreno EC (1987) Selective adsorption of porcine amelogenins onto hydroxyapatite and their inhibitory activity on seeded crystal growth of hydroxyapatite. Calcif Tissue Int 41:281–289
Ashok M, Kalkura SN, Sundaram NM, Arivuoli D (2007) Growth and characterization of hydroxyapatite crystals by hydrothermal method. J Mater Sci Mater Med 18:895–898
Bartlett JD, Simmer JP (1999) Proteinases in developing enamel. Crit Rev Oral Biol Med 10(4):425–441
Bartlett JD, Ryu OH, Xue J, Simmer JP, Margolis HC (1998) Enamelysin mRNA displays a developmentally defined pattern of expression and encodes a protein which degrades amelogenin. Connect Tissue Res 39:405–413
Bartlett JD, Skobe Z, Lee DH, Wright JT, Li Y, Kulkarni AB, Gibson CW (2006) A developmental comparison of matrix metalloproteinase-20 and amelogenin null mouse enamel. Eur J Oral Sci 114(Suppl 1):18–23
Beniash E, Simmer JP, Margolis HC (2005) The effect of recombinant mouse amelogenins on the formation and organization of hydroxyapatite crystals in vitro. J Struct Biol 149(2):182–190
Bennick A (1987) Structural and genetic aspects of proline-rich proteins. J Dent Res 66(2):457–461
Bourd-Boittin K, Fridman R, Fanchon S, Septier D, Goldberg M, Menashi S (2005) Matrix metalloproteinase inhibition impairs the processing, formation and mineralization of dental tissues during mouse molar development. Exp Cell Res 304(2):493–505
Busch S (2004) Regeneration of human tooth enamel. Angew Chem Int Ed Engl 43:1428–1431
Busch S, Schwarz U, Kniep R (2001) Morphogenesis and structure of human teeth in relation to biomimetically grown fluorapatite-gelatine composites. Chem Mater 13:3260–3271
Bush V (1945) Science: the endless frontier: a report to the President by Vannevar Bush, Director of the Office of Scientific Research and Development. United States Government Printing Office, Washington, DC
Cai Y, Liu Y, Yan W, Hu Q, Tao J, Zhang M, Shi Z, Tang R (2007) Role of hydroxyapatite nanoparticle size in bone cell proliferation. J Mater Chem 17:3780
Caterina JJ, Skobe Z, Shi J, Dang Y, Simmer JP, Birkedal-Hansen H, Bartlett JD (2002) Enamelysin (MMP-20) deficient mice display an amelogenesis imperfecta phenotype. J Biol Chem 277(51):49598–49604
Cölfen H, Mann S (2003) Higher-order organization by mesoscale self-assembly and transformation of hybrid nanostructures. Angew Chem Int Ed 42:2350–2365
Collier PM, Sauk JJ, Rosenbloom SJ, Yuan ZA, Gibson CW (1997) An amelogenin gene defect associated with human x-linked amelogenesis imperfecta. Arch Oral Biol 42:235–242
Ćosić I, Pirogova E (2007) Bioactive peptide design using the resonant recognition model. Nonlinear Biomed Phys 1:1–17
De Trad CH, Fang Q, Ćosić I (2000) The resonant recognition model (RRM) predicts amino acid residues in highly conservative regions of the hormone prolactin (PRL). Biophys Chem 84(2):149–157
Delak K, Harcup C, Lakshminarayanan R, Sun Z, Fan Y, Moradian-Oldak J, Evans JS (2009) The tooth enael protein, porcine amelogenin, is an intrinsically disordered protein with an extended molecular configuration in the monomeric form. Biochemistry 48(10):2272–2281
Delgado S, Girondot M, Sire JY (2005) Molecular evolution of amelogenin in mammals. J Mol Evol 60:12–30
Eppell SJ, Tong W, Katz JL, Kuhn L, Glimcher MJ (2001) Shape and size of isolated bone mineralites measured using atomic force microscopy. J Orthop Res 19:1027–1034
Eswar N, Ramakrishnan C, Srinivasan N (2003) Stranded in isolation: structural role of isolated extended strands in proteins. Protein Eng 16(5):331–339
Fong H, White SN, Paine ML, Luo W, Snead ML, Sarikaya M (2003) Enamel structure properties controlled by engineered proteins in transgenic mice. J Bone Miner Res 18(11):2052–2059
Garant PR (2003) Oral cells and tissues. Quintessence, Carol Stream
Gergely C, Szalontai B, Moradian-Oldak J, Cuisinier F (2007) Polyelectrolyte-mediated adsorption of amelogenin monomers and nanospheres forming mono- or multilayers. Biomacromolecules 8:2228–2236
Gibson CW, Yuan Z-A, Hall B, Longenecker G, Cheng E, Thyagarajan T, Sreenath T, Wright JT, Decker S, Piddington R, Harrison G, Kulkami AB (2001) Molecular basis of cell and developmental biology. J Biol Chem 276(34):31871–31875
Gower LB (2008) Biomimetic model systems for investigating the amorphous precursor pathway and its role in biomineralization. Chem Rev 108(11):4551–4627
Habelitz S, Kullar A, Marshall SJ, DenBesten PK, Balooch M, Marshall GW, Li W (2004) Amelogenin-guided crystal growth on fluoroapatite glass-ceramics. J Dent Res 83(9):698–702
Habelitz S, DenBesten PK, Marshall SJ, Marshall GW, Li W (2005a) Amelogenin control over apatite crystal growth is affected by the pH and degree of ionic saturation. Orthod Craniofac Res 8:232–238
Habelitz S, DenBesten PK, Marshall SJ, Marshall GW, Li W (2005b) Amelogenin control over apatite crystal growth is affected by the pH and degree of ionic saturation. Orthod Craniofacial Res 8:232–238
Hamedi M, Elfwing A, Gabrielsson R, Inganäs O (2012) Electronic polymers and DNA self-assembled in nanowire transistors. Small 9:363–368
Hart PS, Hart TC, Michalec MD, Ryu OH, Simmons D, Hong S, Wright JT (2004) Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J Med Genet 41:545–549
Horst J, Samudrala R (2009) Diversity of protein structures and difficulties in fold recognition: the curious case of protein G. F111 Biol Reports 14(1):69
Iijima M, Moradian-Oldak J (2005) Control of apatite crystal growth in a fluoride containing amelogenin-rich matrix. Biomaterials 26(13):1595–1603
Iijima M, Du C, Abbott C, Doi Y, Moradian-Oldak J (2006) Control of apatite crystal growth by the co-operative effect of a recombinant porcine amelogenin and fluoride. Eur J Oral Sci 114(Suppl 1):304–307
Jevtić M, Uskoković D (2007) Influence of urea as a homogenous precipitation agent on sonochemical hydroxyapatite synthesis. Mater Sci Forum 555:285–290
Kashchiev D (2000) Nucleation: basic theory with applications. Butterworth-Heinemann, Oxford
Lakshminarayanan R, Yoon I, Hegde BG, Fan D, Du C, Moradian-Oldak J (2009) Analysis of secondary structure and self-assembly of amelogenin by variable temperature circular dichroism and isothermal titration calorimetry. Proteins 76(3):560–569
Lindemeyer RG, Gibson CW, Wright TJ (2010) Amelogenesis imperfecta due to a mutation of the enamelin gene: clinical case with genotype-phenotype correlations. Pediatr Dent 32(1):56–60
Liu Q, Song C, Wang ZG, Li N, Ding B (2013) Precise organization of metal nanoparticles on DNA origami template. Methods. pii: S1046–2023(13)00402-7. doi:10.1016/j.ymeth.2013.10.006. [Epub ahead of print]
Lyaruu DM, Medina JF, Sarvide S, Bervoets TJ, Everts V, Denbesten P, Smith CE, Bronckers AL (2014) Barrier formation: potential molecular mechanism of enamel fluorosis. J Dent Res [Epub ahead of print]
Mann S (2001) Biomineralization: principles and concepts in bioinorganic materials chemistry. Oxford University Press, Oxford
Margolis HC, Beniash E, Fowler CE (2006) Role of macromolecular assembly of enamel matrix proteins in enamel formation. J Dent Res 85(9):775–793
Martinez-Avila O, Wu S, Kim SJ, Cheng Y, Khan F, Samudrala R, Sali A, Horst JA, Habelitz S (2012) Self-assembly of filamentous amelogenin requires calcium and phosphate: from dimers via nanoribbons to fibrils. Biomacromolecules 13(11):3494–3502
Masuya H, Shimizu K, Sezutsu H, Sakuraba Y, Nagano J, Shimizu A, Fujimoto N, Kawai A, Miura I, Kaneda H, Kobayashi K, Ishijima J, Maeda T, Gondo Y, Noda T, Wakana S, Shiroishi T (2005) Enamelin (Enam) is essential for amelogenesis: ENU-induced mouse mutants as models for different clinical subtypes of human amelogenesis imperfecta (AI). Hum Mol Genet 14(5):575–583
Moradian-Oldak J, Gharakhanian N, Jimenez I (2002a) Limited proteolysis of amelogenin: toward understanding the proteolytic processes in enamel extracellular matrix. Connect Tissue Res 43(2):450–455
Moradian-Oldak J, Bouropoulos N, Wang L, Gharakhanain N (2002b) Analysis of self-assembly and apatite binding properties of amelogenin proteins lacking the hydrophilic C-terminal. Matrix Biol 21(2):197–205
Murakami M (1995) Critical amino acids responsible for conferring calcium channel characteristics are located on the surface and around beta-turn potentials of channel proteins. J Protein Chem 14(3):111–114
Nelson DL, Cox MM (2004) Lehninger principles of biochemistry, 4th edn. W. H. Freeman, New York
Paine ML, Zhu DH, Luo W, Bringas P Jr, Goldberg M, White SN, Lei YP, Sarikaya M, Fong HK, Snead ML (2000) Enamel biomineralization defects result from alterations to amelogenin self-assembly. J Struct Biol 132(3):191–200
Paine ML, Lei YP, Dickerson K, Snead ML (2002) Altered amelogenin self-assembly based on mutations observed in human X-linked Amelogenesis Imperfecta (AIH1). J Biol Chem 277(19):17112–17116
Paine ML, Wang HJ, Luo W, Krebsbach PH, Snead ML (2003) A transgenic animal model resembling amelogenesis imperfecta related to ameloblastin overexpression. J Biol Chem 278(21):19447–19452
Petta V, Moradian-Oldak J, Yannopoulos SN, Bouropoulos N (2006) Dynamic light scattering study of an amelogenin gel-like matrix in vitro. Eur J Oral Sci 114(Suppl 1):308–314
Rath A, Davidson AR, Deber CM (2005) The structure of ‘Unstructured’ regions in peptides and proteins: role of the polyproline II helix in protein folding and recognition. Biopolymers 80:179–185
Ravindranath RM, Devarajan A, Bringas P Jr (2007) Enamel formation in vitro in mouse molar explants exposed to amelogenin polypeptides ATMP and LRAP on enamel development. Arch Oral Biol 52(12):1161–1171
Renugopalakrishnan V, Prabhakaran M, Huang SG, Balasubramaniam A, Strawich E, Glimcher MJ (1989) Secondary structure and limited three-dimensional structure of bovine amelogenin. Connect Tissue Res 22(1–4):131–138
Robinson C (moderator) (2006) Discussion of session 8: amelogenin assembly and function. Eur J Oral Sci 114 (Suppl 1):327–329
Sasaki S, Tagaki T, Suzuki M (1991) Cyclical changes in pH in bovine developing enamel as sequential bands. Arch Oral Biol 36:227–231
Sawada T, Sekiguchi H, Uchida T, Yamashita H, Shintani S, Yanagisawa T (2011) Histological and immunohistochemical analyses of molar tooth germ in enamelin-deficient mouse. Acta Histochem 113(5):542–546
Shaw WJ, Campbell AA, Paine ML, Snead ML (2004) The COOH terminus of the amelogenin, LRAP, is oriented next to the hydroxyapatite surface. J Biol Chem 279(39):40263–40266
Simmer JP, Hu JC-C (2002) Expression, structure, and function of enamel proteinases. Connect Tissue Res 43(2):441–449
Sire JY, Delgado S, Forementin D, Girondot M (2005) Amelogenin: lessons from evolution. Arch Oral Biol 50(2):205–212
Snead ML (2003) Amelogenin protein exhibits a modular design: implications for form and function. Connect Tissue Res 44(1):47–51
Stapley BJ, Creamer TP (1999) A survey of left-handed polyproline II helices. Protein Sci 8(3):587–595
Stephanopoulos G, Garefalaki M-E, Lyroudia K (2005) Genes and related proteins involved in amelogenesis imperfecta. J Dent Res 84(12):1117–1126
Stupp SI, Braun PV (1997) Molecular manipulation of microstructures: biomaterials, ceramics, and semiconductors. Science 277:1242–1248
Tanimoto K, Le T, Zhu L, Witkowska HE, Robinson S, Hall S, Hwang P, DenBesten P, Li W (2008a) Reduced amelogenin-MMP20 interactions in amelogenesis imperfecta. J Dent Res 87(5):451–455
Tanimoto K, Le T, Zhu L, Chen J, Featherstone JDB, Li W, DenBesten P (2008b) Effects of fluoride on the interactions between amelogenin and apatite crystals. J Dent Res 87:39–44
Tarasevich BJ, Howard CJ, Larson JL, Snead ML, Simmer JP, Paine M, Shaw WJ (2007) The nucleation and growth of calcium phosphate by amelogenin. J Crystal Growth 304(2):407–415
The Holy Bible (1609) King James Edition, John 12:24
Uskoković V (2008) Insights into morphological nature of precipitation of cholesterol. Steriods 73:356–369
Uskoković V (2010) Prospects and pits on the path of biomimetics: the case of tooth enamel. J Biomimetics Biomater Tissue Eng 8:45–78
Uskoković V (2013) Entering the era of nanoscience: time to be so small. J Biomed Nanotechnol 9:1441–1470
Uskoković V, Drofenik M (2005) Synthesis of materials within reverse micelles. Surf Rev Lett 12(2):239–277
Uskoković V, Kim M-K, Li W, Habelitz S (2008) Enzymatic processing of amelogenin during continuous crystallization of apatite. J Mater Res 32:3184–3195
Uskoković V, Odsinada R, Djordjevic S, Habelitz S (2011a) Dynamic light scattering and zeta potential of colloidal mixtures of amelogenin and hydroxyapatite in calcium and phosphate rich ionic milieus. Arch Oral Biol 56:521–532
Uskoković V, Li W, Habelitz S (2011b) Amelogenin as a promoter of nucleation and crystal growth of apatite. J Crystal Growth 316:106–117
Uskoković V, Li W, Habelitz S (2011c) Biomimetic precipitation of uniaxially grown calcium phosphate crystals from full-length human amelogenin sols. J Bionic Eng 8(2):114–121
Uskoković V, Khan F, Liu H, Witkowska HE, Zhu L, Li W, Habelitz S (2011d) Proteolytic hydrolysis of amelogenin by means of matrix metalloprotease-20 accelerates mineralization in vitro. Arch Oral Biol 56(12):1548–1559
Wagner RS, Ellis WC (1964) Vapor-liquid-solid mechanism of single crystal growth. Appl Phys Lett 4(5):89–90
Wang HJ, Tannukit S, Zhu DH, Snead ML, Paine ML (2005) Enamel matrix protein interactions. J Bone Miner Res 20(6):1032–1040
Wang L, Guan X, Yin H, Moradian-Oldak J, Nancollas GH (2008) Mimicking the self-organized microstructure of tooth enamel. J Phys Chem C 112(15):5892–5899
Weaver ML, Qiu SR, Hoyer JR, Casey WH, Nancollas GH, De Yoreo JJ (2009) Surface aggregation of urinary proteins and aspartic Acid-rich peptides on the faces of calcium oxalate monohydrate investigated by in situ force microscopy. Calcif Tissue Int 84(6):462–473
Wen HB, Moradian-Oldak J, Fincham AG (2000) Dose-dependent modulation of octacalcium phosphate crystal habit by amelogenins. J Dent Res 79(11):1902–1906
Young KL, Ross MB, Blaber MG, Rycenga M, Jones MR, Zhang C, Senesi AJ, Lee B, Schatz GC, Mirkin CA (2014) Using DNA to design plasmonic metamaterials with tunable optical properties. Adv Mater 26:653–659. doi:10.1002/adma.201302938
Zhang Y, Yan Q, Li W, DenBesten PK (2006) Fluoride down-regulates the expression of matrix metalloproteinase-20 in human fetal tooth ameloblast-lineage cell in vitro. Eur J Oral Sci 114(Suppl 1):105–110
Zhaohua G, Caixia L, Hong Y, Yu X, Yingliang W, Wenxin L, Tao X, Jiuping D (2008) A residue at the cytoplasmic entrance of BK-type channels regulating single-channel opening by its hydrophobicity. Biophys J 94(9):3714–3725
Zheng S, Tu AT, Renugopalakrishnan V, Strawich E, Glimcher MJ (1987) A mixed beta-turn and beta-sheet structure for bovine tooth enamel amelogenin: Raman spectroscopic evidence. Biopolymers 26(10):1809–1813
Zhu L, Uskoković V, Le T, DenBesten P, Huang YL, Habelitz S, Li W (2011) Altered self-assembly and apatite binding of amelogenin induced by N-terminal proline mutation. Arch Oral Biol 56(4):331–336
Acknowledgments
Writing of this chapter was supported by the National Institute of Health grant R00-DE021416. The author thanks Irena Ćosić and Elena Pigorova of the Royal Melbourne Institute of Technology for performing the CWT-RRM analysis of human amelogenin.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Uskoković, V. (2015). Amelogenin in Enamel Tissue Engineering. In: Bertassoni, L., Coelho, P. (eds) Engineering Mineralized and Load Bearing Tissues. Advances in Experimental Medicine and Biology, vol 881. Springer, Cham. https://doi.org/10.1007/978-3-319-22345-2_13
Download citation
DOI: https://doi.org/10.1007/978-3-319-22345-2_13
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-22344-5
Online ISBN: 978-3-319-22345-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)