Amelogenin Exon 5 Peptide Promotes Cell Proliferation and Osteogenic Differentiation in Human Dental Pulp Stem Cells

Amelogenin is a complex enamel matrix protein that consists of various molecular-size proteins and amino acids. A spliced form of amelogenin was identified that included exons 2, 3, 5, 6, and 7. However, the biological function of amelogenin exon 5 on dental pulp remains unknown. We designed a synthetic amelogenin exon 5 encoded peptide (SP), which was based on a protein produced by cells in response to the enamel matrix derivative (EMD). We investigated the effect of the SP on potentiation of osteogenesis and its signal pathway in dental pulp stem cells (DPSCs). DPSCs are an important cell for pulp tissue homeostasis. DPSCs were cultured with SP to examine the effect of cell proliferation and osteogenic differentiation. We also investigated the mitogen-activated protein kinase (MAPK) signaling pathway. SP significantly enhanced cell proliferation and the expression of osteogenic differentiation. Moreover, SP promoted the expression of the MAPK signaling pathway. Therefore, amelogenin exon 5 might contribute to dental pulp capping.

[1]  K. Matsumoto,et al.  Immunohistochemical Characterization of Rapid Dentin Formation Induced by Enamel Matrix Derivative , 2004, Calcified Tissue International.

[2]  Y. Kudo,et al.  Possible involvement of extracellular signal-regulated kinases 1/2 in mitogenic response of periodontal ligament cells to enamel matrix derivative. , 2002, European journal of oral sciences.

[3]  M. Umeda,et al.  The Effects of Synthetic Oligopeptide Derived from Enamel Matrix Derivative on Cell Proliferation and Osteoblastic Differentiation of Human Mesenchymal Stem Cells , 2014, International journal of molecular sciences.

[4]  A. Boyde,et al.  Stem Cell Properties of Human Dental Pulp Stem Cells , 2002, Journal of dental research.

[5]  J. Aubin,et al.  Osteoblast and chondroblast differentiation. , 1995, Bone.

[6]  K. Min,et al.  Combined effects of simvastatin and enamel matrix derivative on odontoblastic differentiation of human dental pulp cells. , 2013, Journal of endodontics.

[7]  L. Hammarström,et al.  Periodontal regeneration in a buccal dehiscence model in monkeys after application of enamel matrix proteins. , 1997, Journal of clinical periodontology.

[8]  Y. Yamaguchi,et al.  Effect of enamel matrix derivative on the differentiation of C2C12 cells. , 2002, Journal of periodontology.

[9]  K. Tanne,et al.  Amelogenin enhances the proliferation of cementoblast lineage cells. , 2011, Journal of periodontology.

[10]  Jukka Westermarck,et al.  Phosphatase‐mediated crosstalk between MAPK signaling pathways in the regulation of cell survival , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  M. Dard,et al.  Recombinant amelogenin regulates the bioactivity of mouse cementoblasts in vitro , 2018, International Journal of Oral Science.

[12]  D. Keskin,et al.  Evaluation of human dental pulp stem cells behavior on a novel nanobiocomposite scaffold prepared for regenerative endodontics. , 2019, Materials science & engineering. C, Materials for biological applications.

[13]  I. Sekiya,et al.  Effect of cell culture density on dental pulp-derived mesenchymal stem cells with reference to osteogenic differentiation , 2019, Scientific Reports.

[14]  G. Rodan,et al.  Different pattern of alkaline phosphatase, osteopontin, and osteocalcin expression in developing rat bone visualized by in situ hybridization , 1990, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[15]  A. Catling,et al.  Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: a perspective. , 2007, Cellular signalling.

[16]  C. Sorenson,et al.  Role of angiogenesis in endodontics: contributions of stem cells and proangiogenic and antiangiogenic factors to dental pulp regeneration. , 2015, Journal of endodontics.

[17]  M. Umeda,et al.  A synthetic oligopeptide derived from enamel matrix derivative promotes the differentiation of human periodontal ligament stem cells into osteoblast-like cells with increased mineralization. , 2013, Journal of periodontology.

[18]  K. Matsumoto,et al.  The induction of reparative dentine by enamel proteins. , 2002, International endodontic journal.

[19]  Makoto Umeda,et al.  The Enhancing Effects of Amelogenin Exon 5-Encoded Peptide from Enamel Matrix Derivative on Odontoblast-Like KN-3 Cells , 2018, Applied Sciences.

[20]  H. Höhling,et al.  Aspects of collagen mineralization in hard tissue formation. , 2005, International review of cytology.

[21]  S. Nomura,et al.  In situ hybridization of bone matrix proteins in undecalcified adult rat bone sections. , 1992, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[22]  Y. Kato,et al.  Effects of human full-length amelogenin on the proliferation of human mesenchymal stem cells derived from bone marrow , 2010, Cell and Tissue Research.

[23]  Yuming Zhao,et al.  Effects of the enamel matrix derivative on the proliferation and odontogenic differentiation of human dental pulp cells. , 2014, Journal of dentistry.

[24]  M. Takagi,et al.  Gene Expression and Immunohistochemical Localization of Osteonectin in Association with Early Bone Formation in the Developing Mandible , 2004, The Histochemical Journal.

[25]  Y. Kato,et al.  Amelogenin Enhances the Osteogenic Differentiation of Mesenchymal Stem Cells Derived from Bone Marrow , 2012, Cells Tissues Organs.

[26]  M. Ueda,et al.  A feasibility of useful cell-based therapy by bone regeneration with deciduous tooth stem cells, dental pulp stem cells, or bone-marrow-derived mesenchymal stem cells for clinical study using tissue engineering technology. , 2010, Tissue engineering. Part A.

[27]  A. Fincham,et al.  Amelogenins. Sequence homologies in enamel-matrix proteins from three mammalian species. , 1983, The Biochemical journal.

[28]  A. Tanaka,et al.  Analysis of eosinophilic round bodies formed after injection of enamel matrix derivative into the backs of rats. , 2005, Journal of periodontology.

[29]  L. Hammarström.  Enamel matrix, cementum development and regeneration. , 1997, Journal of clinical periodontology.

[30]  J. Knowles,et al.  Differential effect of amelogenin peptides on osteogenic differentiation in vitro: identification of possible new drugs for bone repair and regeneration. , 2012, Tissue engineering. Part A.

[31]  A. George,et al.  Two Related Low Molecular Mass Polypeptide Isoforms of Amelogenin Have Distinct Activities in Mouse Tooth Germ Differentiation In Vitro , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  Yanfang Ren,et al.  Effects of Adenosine Triphosphate on Proliferation and Odontoblastic Differentiation of Human Dental Pulp Cells. , 2016, Journal of endodontics.

[33]  H. Hayashi,et al.  Hard Tissue Formation by Human Periodontal Ligament Fibroblast Cells Treated with an Emdogain®-Derived Oligopeptide in vitro , 2012 .

[34]  S. Lyngstadaas,et al.  Amelogenin gene similarity in vertebrates: DNA sequences encoding amelogenin seem to be conserved during evolution , 2004, Journal of Comparative Physiology B.