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Proteinases in Enamel Development

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Extracellular Matrix Biomineralization of Dental Tissue Structures

Part of the book series: Biology of Extracellular Matrix ((BEM,volume 10))

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Abstract

Proteinases are essential for proper enamel formation. During the secretory stage of enamel development, the ameloblasts responsible for enamel formation secrete enamel matrix proteins including amelogenin (AMELX), ameloblastin (AMBN), enamelin (ENAM), and matrix metalloproteinase-20 (MMP20, enamelysin). MMP20 cleaves the enamel matrix proteins soon after they are secreted and these cleavages are essential because the autosomal recessive inheritance of MMP20 mutations can cause severe enamel defects. Later, during the transition to the early maturation stage of enamel development, kallikrein-related peptidase-4 (KLK4) is secreted by ameloblasts. KLK4 facilitates protein removal, which allows the enamel to mature into its final hardened form. Autosomal recessive inheritance of KLK4 mutations can also cause severe enamel defects consisting of soft enamel that easily abrades from teeth. Recently, pre-secretory ameloblasts and secretory stage ameloblasts were demonstrated to express A Disintegrin And Metallopeptidase Domain-10 (ADAM10). Although ADAM10 may facilitate enamel development, mutations are not known to cause enamel defects in humans primarily because its inactivation is likely embryonic lethal as it is in mice. Nonetheless, as discussed below, the ability of ADAM10 to precisely locate on the cell membrane holds exciting possibilities for how cohorts of secretory stage ameloblasts move relative to one another as enamel development progresses.

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References

  • Bartlett JD (2013) Dental enamel development: proteinases and their enamel matrix substrates. ISRN Dent 2013:684607

    PubMed  PubMed Central  Google Scholar 

  • Bartlett JD, Simmer JP (1999) Proteinases in developing dental enamel. Crit Rev Oral Biol Med 10(4):425–441

    Article  CAS  Google Scholar 

  • Bartlett JD, Simmer JP, Xue J, Margolis HC, Moreno EC (1996) Molecular cloning and mrna tissue distribution of a novel matrix metalloproteinase isolated from porcine enamel organ. Gene 183(1–2):123–128

    Article  CAS  Google Scholar 

  • Beniash E, Skobe Z, Bartlett JD (2006) Formation of the dentino-enamel interface in enamelysin (mmp-20)-deficient mouse incisors. Eur J Oral Sci 114(Suppl 1):24–29

    Article  CAS  Google Scholar 

  • Bossen C, Ingold K, Tardivel A, Bodmer JL, Gaide O, Hertig S, Ambrose C, Tschopp J, Schneider P (2006) Interactions of tumor necrosis factor (tnf) and tnf receptor family members in the mouse and human. J Biol Chem. 281(20):13964–13971

    Article  CAS  Google Scholar 

  • Caterina JJ, Skobe Z, Shi J, Ding Y, Simmer JP, Birkedal-Hansen H, Bartlett JD (2002) Enamelysin (matrix metalloproteinase 20)-deficient mice display an amelogenesis imperfecta phenotype. J Biol Chem 277(51):49598–49604

    Article  CAS  Google Scholar 

  • Daculsi G, Menanteau J, Kerebel LM, Mitre D (1984) Length and shape of enamel crystals. Calcif Tissue Int 36(5):550–555

    Article  CAS  Google Scholar 

  • Dempsey PJ (2017) Role of adam10 in intestinal crypt homeostasis and tumorigenesis. Biochim Biophys Acta Mol Cell Res 1864(11 Pt B):2228–2239

    Google Scholar 

  • Fischer T, Riedl R (2020) Challenges with matrix metalloproteinase inhibition and future drug discovery avenues. Expert Opin Drug Discov 1–14

    Google Scholar 

  • Fukae M, Tanabe T, Uchida T, Lee SK, Ryu OH, Murakami C, Wakida K, Simmer JP, Yamada Y, Bartlett JD (1998) Enamelysin (matrix metalloproteinase-20): localization in the developing tooth and effects of ph and calcium on amelogenin hydrolysis. J Dent Res 77(8):1580–1588

    Article  CAS  Google Scholar 

  • Haining EJ, Yang J, Bailey RL, Khan K, Collier R, Tsai S, Watson SP, Frampton J, Garcia P, Tomlinson MG (2012) The tspanc8 subgroup of tetraspanins interacts with a disintegrin and metalloprotease 10 (adam10) and regulates its maturation and cell surface expression. J Biol Chem 287(47):39753–39765

    Article  CAS  Google Scholar 

  • Hu JC, Ryu OH, Chen JJ, Uchida T, Wakida K, Murakami C, Jiang H, Qian Q, Zhang C, Ottmers V et al (2000) Localization of emsp1 expression during tooth formation and cloning of mouse cdna. J Dent Res 79(1):70–76

    Article  CAS  Google Scholar 

  • Hu Y, Smith CE, Richardson AS, Bartlett JD, Hu JC, Simmer JP (2016) Mmp20, klk4, and mmp20/klk4 double null mice define roles for matrix proteases during dental enamel formation. Mol Genet Genomic Med 4(2):178–196

    Article  CAS  Google Scholar 

  • Ikeda A, Shahid S, Blumberg BR, Suzuki M, Bartlett JD (2019) Adam10 is expressed by ameloblasts, cleaves the relt tnf receptor extracellular domain and facilitates enamel development. Sci Rep 9(1):14086

    Article  Google Scholar 

  • Jorissen E, Prox J, Bernreuther C, Weber S, Schwanbeck R, Serneels L, Snellinx A, Craessaerts K, Thathiah A, Tesseur I et al (2010) The disintegrin/metalloproteinase adam10 is essential for the establishment of the brain cortex. J Neurosci 30(14):4833–4844

    Article  CAS  Google Scholar 

  • Jouannet S, Saint-Pol J, Fernandez L, Nguyen V, Charrin S, Boucheix C, Brou C, Milhiet PE, Rubinstein E (2016) Tspanc8 tetraspanins differentially regulate the cleavage of adam10 substrates, notch activation and adam10 membrane compartmentalization. Cell Mol Life Sci 73(9):1895–1915

    Article  CAS  Google Scholar 

  • Kawasaki K, Hu JC, Simmer JP (2014) Evolution of klk4 and enamel maturation in eutherians. Biol Chem 395(9):1003–1013

    Article  CAS  Google Scholar 

  • Kim JW, Zhang H, Seymen F, Koruyucu M, Hu Y, Kang J, Kim YJ, Ikeda A, Kasimoglu Y, Bayram M et al (2019) Mutations in relt cause autosomal recessive amelogenesis imperfecta. Clin Genet 95(3):375–383

    Article  CAS  Google Scholar 

  • Maretzky T, Reiss K, Ludwig A, Buchholz J, Scholz F, Proksch E, de Strooper B, Hartmann D, Saftig P (2005) Adam10 mediates e-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation. Proc Natl Acad Sci USA 102(26):9182–9187

    Article  CAS  Google Scholar 

  • Matthews AL, Szyroka J, Collier R, Noy PJ, Tomlinson MG (2017) Scissor sisters: regulation of adam10 by the tspanc8 tetraspanins. Biochem Soc Trans 45(3):719–730

    Article  CAS  Google Scholar 

  • Matthews AL, Koo CZ, Szyroka J, Harrison N, Kanhere A, Tomlinson MG (2018) Regulation of leukocytes by tspanc8 tetraspanins and the “molecular scissor” adam10. Front Immunol 9:1451

    Article  Google Scholar 

  • Nagano T, Kakegawa A, Yamakoshi Y, Tsuchiya S, Hu JC, Gomi K, Arai T, Bartlett JD, Simmer JP (2009) Mmp-20 and klk4 cleavage site preferences for amelogenin sequences. J Dent Res 88(9):823–828

    Article  CAS  Google Scholar 

  • Nikolopoulos G, Smith CEL, Brookes SJ, El-Asrag ME, Brown CJ, Patel A, Murillo G, O’Connell MJ, Inglehearn CF, Mighell AJ (2020) New missense variants in relt causing hypomineralised amelogenesis imperfecta. Clin Genet 97(5):688–695

    Article  CAS  Google Scholar 

  • Parkin E, Harris B (2009) A disintegrin and metalloproteinase (adam)-mediated ectodomain shedding of adam10. J Neurochem 108(6):1464–1479

    Article  CAS  Google Scholar 

  • Reiss K, Saftig P (2009) The “a disintegrin and metalloprotease” (adam) family of sheddases: physiological and cellular functions. Semin Cell Dev Biol 20(2):126–137

    Article  CAS  Google Scholar 

  • Ronnholm E (1962) An electron microscopic study of the amelogenesis in human teeth. I. The fine structure of the ameloblasts. J Ultrastruct Res 6:229–248

    Article  CAS  Google Scholar 

  • Ryu OH, Fincham AG, Hu CC, Zhang C, Qian Q, Bartlett JD, Simmer JP (1999) Characterization of recombinant pig enamelysin activity and cleavage of recombinant pig and mouse amelogenins. J Dent Res 78(3):743–750

    Article  CAS  Google Scholar 

  • Ryu O, Hu JC, Yamakoshi Y, Villemain JL, Cao X, Zhang C, Bartlett JD, Simmer JP (2002) Porcine kallikrein-4 activation, glycosylation, activity, and expression in prokaryotic and eukaryotic hosts. Eur J Oral Sci 110(5):358–365

    Article  CAS  Google Scholar 

  • Sawada T, Yamamoto T, Yanagisawa T, Takuma S, Hasegawa H, Watanabe K (1990) Evidence for uptake of basement membrane by differentiating ameloblasts in the rat incisor enamel organ. J Dent Res 69(8):1508–1511

    Article  CAS  Google Scholar 

  • Schlöndorff J, Blobel CP (1999) Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding. J Cell Sci 112(Pt 21):3603–3617

    Article  Google Scholar 

  • Simmer JP, Fukae M, Tanabe T, Yamakoshi Y, Uchida T, Xue J, Margolis HC, Shimizu M, DeHart BC, Hu CC et al (1998) Purification, characterization, and cloning of enamel matrix serine proteinase 1. J Dent Res 77(2):377–386

    Article  CAS  Google Scholar 

  • Simmer JP, Hu Y, Lertlam R, Yamakoshi Y, Hu JC (2009) Hypomaturation enamel defects in klk4 knockout/lacz knockin mice. J Biol Chem 284(28):19110–19121

    Article  CAS  Google Scholar 

  • Skobe Z (1977) Enamel rod formation in the monkey observed by scanning electron microscopy. Anat Rec 187(3):329–334

    Article  CAS  Google Scholar 

  • Smith CE, Richardson AS, Hu Y, Bartlett JD, Hu JC, Simmer JP (2011) Effect of kallikrein 4 loss on enamel mineralization: comparison with mice lacking matrix metalloproteinase 20. J Biol Chemi 286(20):18149–18160

    Article  CAS  Google Scholar 

  • Smith CE, Hu Y, Hu JC, Simmer JP (2016) Ultrastructure of early amelogenesis in wild-type, amelx(-/-), and enam(-/-) mice: enamel ribbon initiation on dentin mineral and ribbon orientation by ameloblasts. Mol Genet Genomic Med 4(6):662–683

    Article  CAS  Google Scholar 

  • Smith CEL, Kirkham J, Day PF, Soldani F, McDerra EJ, Poulter JA, Inglehearn CF, Mighell AJ, Brookes SJ (2017) A fourth klk4 mutation is associated with enamel hypomineralisation and structural abnormalities. Front Physiol 8:333

    Article  Google Scholar 

  • Turk BE, Lee DH, Yamakoshi Y, Klingenhoff A, Reichenberger E, Wright JT, Simmer JP, Komisarof JA, Cantley LC, Bartlett JD (2006) Mmp-20 is predominately a tooth-specific enzyme with a deep catalytic pocket that hydrolyzes type v collagen. Biochemistry (Mosc) 45(12):3863–3874

    Article  CAS  Google Scholar 

  • Wang SK, Zhang H, Chavez MB, Hu Y, Seymen F, Koruyucu M, Kasimoglu Y, Colvin CD, Kolli TN, Tan MH et al (2020) Dental malformations associated with biallelic mmp20 mutations. Mol Genet Genomic Med 8(8):e1307

    Article  CAS  Google Scholar 

  • Weber S, Niessen MT, Prox J, Lüllmann-Rauch R, Schmitz A, Schwanbeck R, Blobel CP, Jorissen E, de Strooper B, Niessen CM et al (2011) The disintegrin/metalloproteinase adam10 is essential for epidermal integrity and notch-mediated signaling. Development 138(3):495–505

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Biosciences, The Ohio State University, College of Dentistry, Columbus, OH, USA

    Shifa Shahid & John D. Bartlett

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  1. Shifa Shahid
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  2. John D. Bartlett
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Correspondence to John D. Bartlett .

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Editors and Affiliations

  1. Faculty of Fundamental and Biomedical Sciences, Paris Cite University INSERM UMR-S 1124, Paris, France

    Michel Goldberg

  2. Department of Orofacial Sciences, UCSF School of Dentistry, University of California, San Francisco, USA

    Pamela Den Besten

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Shahid, S., Bartlett, J.D. (2021). Proteinases in Enamel Development. In: Goldberg, M., Den Besten, P. (eds) Extracellular Matrix Biomineralization of Dental Tissue Structures. Biology of Extracellular Matrix, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-030-76283-4_10

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