Recombinant amelogenin regulates the bioactivity of mouse cementoblasts in vitro

Abstract

A protein with its roots in dental development stimulates the proliferation and gene expression of cells linked to regeneration. Amelogenin is a mediator of enamel and tooth root formation, and the main component of a recently-developed medicine for periodontal regeneration. An international research group led by Sema Hakki, of Selcuk University, Turkey, has now elucidated the effects of amelogenin on cementoblasts, a type of cell responsible for producing the vital, mineralized layer on surface of the tooth root. Hakki’s team found that the bacteria-derived amelogenin increased the rate of mouse cementoblast proliferation and mineralization in vitro, and increased the expression of genes related to bone and tissue generation. The team also demonstrated the presence of a likely amelogenin receptor on the cells used in their study. These findings support further investigation into amelogenin’s therapeutic potential.

References

[1] Bosshardt DD. Biological mediators and periodontal regeneration: a review of enamel matrix protein at the cellular and molecular level. J. Clin. Periodontol., 2008, 35(Suppl 8): 87-105.

[2] Lyngstadaas SP, . Enamel matrix proteins; old molecules for new applications. Orthod. Craniofac. Res., 2009, 12: 1-11.

[3] Hakki SS, Berry JE, Somerman MJ. The effect of enamel matrix protein derivative on follicle cells in vitro. J. Periodontol., 2001, 72: 679-687.

[4] Grandin HM, Gemperli-Graf A, Dard M. Enamel matrix derivative: a review of cellular effects in vitro and a model of molecular arrangement and functioning. Tissue Eng. Part B, 2012, 18: 181-202.

[5] Hatakeyama J, . Amelogenin-mediated regulation of osteoclastogenesis, and periodontal cell proliferation and migration. J. Dent. Res., 2006, 85: 144-149.

[6] Zeichner-David M, . Amelogenin and ameloblastin show growth-factor like activity in periodontal ligament cells. Eur. J. Oral Sci., 2006, 114: 244-253. Suppl 1

[7] Miron RJ, . Twenty years of enamel matrix derivative: the past, the present and the future. J. Clin. Periodontol., 2016, 43: 668-683. b

[8] Giannobile WV, Somerman MJ. Growth and amelogenin-like factors in periodontal wound healing. A systematic review. Ann. Periodontol., 2003, 8: 193-204.

[9] Sculean A, . The application of an enamel matrix protein derivative (Emdogain) in regenerative periodontal therapy: a review. Med. Princ. Pract., 2007, 16: 167-180.

[10] Esposito M, . Enamel matrix derivative (Emdogain®) for periodontal tissue regeneration in intrabony defects. A Cochrane systematic review. Eur. J. Oral Implantol., 2009, 2: 247-266.

[11] Rathe F, . The effect of enamel matrix derivative (Emdogain®) on bone formation: a systematic review. Tissue Eng: Part B, 2009, 15: 215-224.

[12] Koop R, Merheb J, Quirynen M. Periodontal regeneration with enamel matrix derivative in reconstructive periodontal therapy: a systematic review. J. Periodontol., 2012, 83: 707-720.

[13] Schmidlin PR. Regenerative treatment of a cemental tear using enamel matrix derivatives:a ten-year follow-up. Open Dent. J., 2012, 6: 148-152.

[14] Matarosso M, . Enamel matrix deriavtive and bone grafts for periodontal regeneration of intrabony defects. A systematic review and meta-analysis. Clin. Oral Invest, 2015, 19: 1581-1593.

[15] Al-Hezaimi K, Al-Askar M, Al-Rasheed A. Characteristics of newly formed cementum following emdogain application. Int. J. Oral Sci., 2011, 3: 21-26.

[16] Bosshardt DD, . Pattern of mineralization after regenerative periodontal therapy with enamel matrix proteins. Eur. J. Oral. Sci., 2006, 114(Suppl 1): 225-231.

[17] Amin HD, . Differential effect of amelogenin peptides on osteogenic differentiation in vitro: identification of possible new drugs for bone repair and regeneration. Tissue Eng. Part A, 2012, 18: 1193-1202.

[18] Fawzy El-Sayed KM, . Effect of Emdogain enamel matrix derivative and BMP-2 on the gene expression and mineralized nodule formation of alveolar bone proper-derived stem/progenitor cells. J. Cranio-Maxillo-Fac. Surg., 2013, 42: 568-576.

[19] Wang Y, Zhao Y, Ge L. Effects of the enamel matrix derivative on the proliferation and odontogenic differentiation of human dental pulp cells. J. Dent., 2014, 42: 53-59.

[20] Miron RJ, . Gene array of primary human osteoblasts exposed to enamel matrix derivative in combination with a natural bone material. Clin. Oral Invest, 2013, 17: 405-410.

[21] Miron RJ, . Effect of enamel matrix derivative liquid on osteoblast and periodontal ligament cell proliferation and differentiation. J. Periodontol., 2016, 87: 91-99.

[22] Frasheri I, . Full-length amelogenin influences the differentiation of human dental pulp stem cells. Stem Cell Res. Ther., 2016, 7: 10.

[23] Wang Z, . In vitro studies on human periodontal ligament stem cell sheets enhanced by enamel matrix derivative. Colloids Surf. B Biointerfaces, 2016, 141: 102-111.

[24] Swanson EC, . Amelogenins regulate expression of genes associated with cementoblasts in vitro. Eur. J. Oral Sci., 2006, 114(Suppl 1): 239-243.

[25] Ruan Q, Moradian-Oldak J. Amelogenin and enamel biomimetics. J. Mater. Chem. B, 2015, 3: 3112-3129.

[26] Bosshardt DD, . Effects of enamel matrix proteins on tissue formation along the roots of human teeth. J. Periodontal. Res., 2005, 40: 158-167.

[27] Tompkins K, George A, Veis A. Characterization of a mouse amelogenin [A-4]/M59 cell surface receptor. Bone, 2006, 38: 172-180.

[28] Shapiro JL, . Cellular uptake of amelogenin, and its localization to CD63, and lamp1-positive vesicles. Cell Mol. Life. Sci., 2007, 64: 244-256.

[29] Gungormus M, . Cementomimetics-constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides. Int. J. Oral Sci., 2012, 4: 69-77.

[30] Simmer JP, . Isolation and characterization of a mouse amelogenin expressed in Escherichia coli. Calcif. Tissue Int., 1994, 54: 312-319.

[31] Deutsch D, . Regeneration of the periodontal tissues in vivo using the recombinant human amelogenin protein. J. Dent. Res., 2003, 82: 292.

[32] Taylor AL, . High yield of biologically active recombinant human amelogenin using the baculovirus expression system. Protein Expr. Purif., 2006, 45: 43-53.

[33] Haze A, . Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis. J. Cell Mol. Med., 2009, 13: 1110-1124.

[34] Li W, . X-linked amelogenesis imperfecta may result from decreased formation of tyrosine rich amelogenin peptide (TRAP). Arch. Oral Biol., 2003, 48: 177-183.

[35] Svensson J, . Histidine tag fusion increases expression levels of active recombinant amelogenin in Escherichia coli. Protein Expr. Purif., 2006, 48: 134-141.

[36] Mounir MM, Matar MA, Snead ML. Recombinant amelogenin protein induces apical closure and pulp regeneration in open-apex, nonvital permanent canine teeth. J. Endod., 2016, 42: 402-412.

[37] Bosshardt DD. Are cementoblasts a subpopulation of osteoblasts or a unique phenotype?. J. Dent. Res., 2005, 84: 390-406.

[38] D’Errico JA, . Employing a transgenic animal model to obtain cementoblasts in vitro. J. Periodontol., 2000, 71: 63-72.

[39] Tokiyasu Y, . Enamel factors regulate expression of genes associated with cementoblasts. Periodontolgy, 2000, 71: 1829-1839.

[40] Viswanathan HL, . Amelogenin: a potential regulator of cementum-associated genes. J. Periodontol., 2003, 74: 1423-1431.

[41] Boabaid F, . Leucine-rich amelogenin peptide: a candidate signaling molecule during cementogenesis. J. Periodontol., 2004, 75: 1126-1136.

[42] Kunimatsu R, . Amelogenin enhances the proliferation of cementoblast lineage cells. J. Periodontol., 2011, 82: 1632-1638.

[43] Yoshimi Y, . Effects of C-terminal amelogenin peptide on proliferation of human cementoblast lineage cells. J. Periodontol., 2016, 87: 820-827.

[44] Tanimoto K, . Differential effects of amelogenin on mineralization of cementoblasts and periodontal ligament cells. J. Periodontol., 2012, 83: 672-679.

[45] Veis A, . Specific amelogenin gene splice products have signaling effects on cells in culture and in implants in vivo. J. Biol. Chem., 2000, 275: 41263-41272.

[46] Warotayanont R, . Leucine-rich amelogenin peptide induces osteogenesis in mouse embryonic stem cells. Biochem. Biophys. Res. Commun., 2008, 367: 1-6.

[47] Warotayanont R, . Leucine-rich amelogenin peptide induces osteogenesis by activation of the wnt pathway. Biochem. Biophys. Res. Commun., 2009, 387: 558-563.

[48] Johnson DL, . Cellular effects of enamel matrix derivative are associated with different molecular weight fractions following separation by size-exclusion chromatography. J. Periodontol., 2009, 80: 648-656.

[49] Jue SS, . The effects of enamel matrix derivative on the proliferation and differentiation of human mesenchymal stem cells. Clin. Oral Implants Res., 2010, 21: 741-746.

[50] Jingchao H, . Human amelogenin up-regulates osteogenic gene expression in human bone marrow stroma cells. Biochem Biophys. Res. Comm., 2011, 408: 437-441.

[51] Izumikawa M, . Effects of amelogenin on proliferation, differentiation, and mineralization of rat bone marrow mesenchymal stem cells in vitro. Sci. World J., 2012, 2012: 879731.

[52] Miron RJ, . Gene array of primary human osteoblasts exposed to enamel matrix derivative in combination with natural bone mineral. Clin. Oral Invest., 2013, 17: 405-410.

[53] Vrtačnik P, Marc J, Ostanek B. Epigenetic mechanisms in bone. Clin. Chem. Lab. Med., 2014, 52: 589-608.

[54] Arzate H, Zeichner-David M, Mercado-Celis G. Cementum proteins: role in cementogenesis, biomineralization, periodontium formation and regeneration. Periodontology, 2015, 67: 211-233.

[55] Zhang H, . Full length amelogenin binds to cell surface LAMP-1 on tooth root/periodontium associated cells. Arch. Oral Biol., 2010, 55: 417-425.

[56] Almqvist S, . Amelogenin is phagocytized and induves changes in integrin configuration, gene expression and prolferation of cultured normal human dermal fibroblasts. J. Mater. Sci. Mater. Med., 2010, 21: 947-954.

[57] Gassmann G, . Influence of enamel matrix derivative on primary CD4+ T-helper lymphocyte migration, CD25 activation, and apoptosis. J. Periodontol., 2009, 80: 1524-1533.

[58] Svensson Bonde J, Bulow L. One-step purification of recombinant human amelogenin and use of amelogenin as a fusion partner. PLoS ONE, 2012, 7: e33269.

[59] Hakki SS, . Bone morphogenetic protein-7 enhances cementoblast function in vitro. J. Periodontol., 2010, 81: 1663-1674.

[60] Butler SJ, Bülow L, Bonde J. Functionalization of recombinant amelogenin nanospheres allows their binding to cellulose materials. Biotechnol. J., 2016, 11: 1343-1351.

[61] Chen D, . Osteoblastic cell lines derived from a transgenic mouse containing the osteocalcin promoter driving SV T-antigen. Mol. Cell Differ., 1995, 3: 193-212.

[62] Hakki SS, Korkusuz P, Purali N, Bozkurt B, Kus M, Duran I. Attachment, proliferation and collagen type I mRNA expression of human gingival fibroblasts on different biodegradable membranes. Connect Tissue Res, 2013, 54: 260-226.