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 behavio...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.展开更多
In the canonical version of evolution by gene duplication, one copy is kept unaltered while the other is free to evolve. This process of evolutionary experimentation can persist for millions of years. Since it is so s...In the canonical version of evolution by gene duplication, one copy is kept unaltered while the other is free to evolve. This process of evolutionary experimentation can persist for millions of years. Since it is so short lived in comparison to the lifetime of the core genes that make up the majority of most genomes, a substantial fraction of the genome and the transcriptome may—in principle—be attributable to what we will refer to as "evolutionary transients", referring here to both the process and the genes that have gone or are undergoing this process. Using the rice gene set as a test case, we argue that this phenomenon goes a long way towards explaining why there are so many more rice genes than Arabidopsis genes, and why most excess rice genes show low similarity to eudicots.展开更多
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)+2 种基金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 Awardthe NIH,National Institute of Dental and Craniofacial Research Ruth L. Kirschstein Individual pre-doctoral dental scientist fellowship, 5F30DE01752
文摘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.
基金supported by Chinese Academy of Sciences (Grants No. GJHZ0701-6 and KSCX2-YWN-023)National Natural Science Foundation of China (Grants No. 30725008, 90403130, 90608010, 30221004, 90612019, and 30392130)+4 种基金the "973" Program (Grants No. 2006CB910400, 2007CB815701, 2007CB815703, and 2007CB815705)the "863" Program (Grants No. 2006AA02Z334, 2006AA10A121, and 2006AA02Z177)Beijing Municipal Science and Technology Commission (Grant No. D07030200740000)Danish Platform for Integrative Biology, Danish Natural Science Research Council, Danish Research Council, the Solexa Project (Grant No. 272-07-0196)National Science Foundation of USA (Grant No. DBI 0217241)
文摘In the canonical version of evolution by gene duplication, one copy is kept unaltered while the other is free to evolve. This process of evolutionary experimentation can persist for millions of years. Since it is so short lived in comparison to the lifetime of the core genes that make up the majority of most genomes, a substantial fraction of the genome and the transcriptome may—in principle—be attributable to what we will refer to as "evolutionary transients", referring here to both the process and the genes that have gone or are undergoing this process. Using the rice gene set as a test case, we argue that this phenomenon goes a long way towards explaining why there are so many more rice genes than Arabidopsis genes, and why most excess rice genes show low similarity to eudicots.