Cementomimetics——constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides  

作　　者：Mustafa Gungormus Ersin E Oren Jeremy A Horst Hanson Fong Marketa Hnilova Martha J Somerman Malcolm L Snead Ram Samudrala Candan Tamerler Mehmet Sarikaya 

机构地区：[1]Genetically Engineered Materials Science and Engineering Center,and Department of Materials Science and Engineering,University of Washington,Seattle,USA [2]Departmentof Orofacial Sciences,University of California at San Francisco,San Francisco,USA [3]Laboratory of Oral Connective Tissue Biology,National Institute of Arthritis and Musculoskeletal and Skin Diseases,National Institutes of Health,Bethesda,USA [4]Center for Craniofacial Molecular Biology,Ostrow School of Dentistry of the University of Southern California,Los Angeles,USA [5]Department of Microbiology,University of Washington,Seattle,USA

出　　处：《International Journal of Oral Science》2012年第2期69-77,共9页国际口腔科学杂志（英文版）

基　　金：The research was mainly supported by NSF-MRSEC (DMR# 0520567) at the University of Washington (MG, MH, HF, RS, EEO, CT and MS);by NIH,National Institute of Dental and Craniofacial Research grant DE13045 (MLS);grant DE15109 to MJS (The studies described here were completed while MJS was at the University of Washington);JAH was supported by the University of Washington, Warren G. Magnuson Scholars Award;the NIH,National Institute of Dental and Craniofacial Research Ruth L. Kirschstein Individual pre-doctoral dental scientist fellowship, 5F30DE01752

摘　　要：Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides （HABPs） previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 （ADP5） was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein-mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure-function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbiditv associated with tooth loss.Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides （HABPs） previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 （ADP5） was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein-mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure-function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbiditv associated with tooth loss.

关 键 词：AMELOGENIN amelogenin-derived peptides bioinformatics biomineralization cementomimetics CEMENTUM demineral-ization REMINERALIZATION 

分 类 号：R780.2[医药卫生—口腔医学]