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
The tooth root cementum is a thin, mineralized tissue covering the root dentin that is present primarily as acellular cementum on the cervical root and cellular cementum covering the apical root. While cementum shares...The tooth root cementum is a thin, mineralized tissue covering the root dentin that is present primarily as acellular cementum on the cervical root and cellular cementum covering the apical root. While cementum shares many properties in common with bone and dentin, it is a unique mineralized tissue and acellular cementum is critical for attachment of the tooth to the surrounding periodontal ligament （PDL）. Resources for methodologies for hard tissues often overlook cementum and approaches that may be of value for studying this tissue. To address this issue, this report offers detailed methodology, as well as comparisons of several histological and immunohistochemical stains available for imaging the cementum-PDL complex by light microscopy. Notably, the infrequently used Alcian blue stain with nuclear fast red counterstain provided utility in imaging cementum in mouse, porcine and human teeth. While no truly unique extracellular matrix markers have been identified to differentiate cementum from the other hard tissues, immunohistochemistry for detection of bone sialoprotein （BSP）, osteopontin （OPN）, and dentin matrix protein 1 （DMP1） is a reliable approach for studying both acellular and cellular cementum and providing insight into developmental biology of these tissues. Histoloeical and immunohistochemical aooroaches Drovide insight on developmental biology of cementum.展开更多
Periodontal regenerative techniques have been proposed; however, the outcomes remain debatable. The present investigation assessed the regenerated cementum following enamel matrix derivative application in dehiscence-...Periodontal regenerative techniques have been proposed; however, the outcomes remain debatable. The present investigation assessed the regenerated cementum following enamel matrix derivative application in dehiscence-type defects. Buccal osseous dehiscences were surgically created on the maxillary cuspid, and the second and fourth premolars in five female beagle dogs. The treatment group （n=15 sites） received the enamel matrix derived application, whereas the control groups （n=15） did not. The dogs were sacrificed 4 months following treatment and the specimens were histologically and histometrically examined. The newly formed cementum was uneven in thickness and mineralization, overlapped the old cementum and exhibited functional orientation, cementocyte lacunae and collagen fibril bundles. Most of the histological specimens showed the presence of a gap between the newly formed cementum and the underlying dentin. Control sites did not exhibit any cementum formation. The present study concluded that newly formed cementum is of cellular type and exhibits multiple characteristics.展开更多
Determining the microstructure in human cementum might help us design new kinds of replacement materials for the treatment of teeth injury and disease. The authors characterized the nanostructures in the cementum of h...Determining the microstructure in human cementum might help us design new kinds of replacement materials for the treatment of teeth injury and disease. The authors characterized the nanostructures in the cementum of health human teeth via scanning electronic microscopy（SEM）. It was found that the acellular cementum is mainly composed of two kinds of nanostructures―inorganic nanoparticles and organic nanofibers. And the inorganic nanoparticles show a tendency to arrange along the organic nanofibers. Based on the micro-molding in capillary strategy, the distribution of organic component in acellular cementum was copied with UV curable resin. After removing the inorganic nanoparticles by acid etching, many isolated spindle shape nanopores were left in polymer, which su- ggested that the inorganic nanoparticles should have been isolated by the organic component in cementum, and should be oval or nanosheet in shape. We hope the present work could provide reference for the biomimetic preparation of tissue engineering materials, and help us design new types of tooth implant.展开更多
In this paper, the elastic modulus measuring of human cementum is studied. The average value of the elastic modulus measured from 100 specimens is E = 2.398 +/- 0.455 GPa. The specimens were made from incisors, canine...In this paper, the elastic modulus measuring of human cementum is studied. The average value of the elastic modulus measured from 100 specimens is E = 2.398 +/- 0.455 GPa. The specimens were made from incisors, canines, bicuspids, and molars. The testing was done on type AG-10TA electronic-mechanical universal material testing machine. It was verified by mathematical statistics that the probability distribution of measured data obeys normal distribution. By the great difference in elastic moduli between cementum and dentin it is explained that 1. why more cementum grows at the root apexes; 2. the behavior of cementum must be taken into consideration when the stress analysis for teeth is carried out.展开更多
Seasonality study of Paleolithic archaeological faunal assemblages is important for reconstructing modes of animal death and ancient hominin strategies for prey acquisition. The dental cementum of animal teeth records...Seasonality study of Paleolithic archaeological faunal assemblages is important for reconstructing modes of animal death and ancient hominin strategies for prey acquisition. The dental cementum of animal teeth records the season of an individual animal in which it died, providing the necessary evidence for determining any patterns in season of death. This article presents the procedure and preliminary results of the application of cementum incremental analysis to equid teeth, which comprise the dominant component of the fauna from the Xujiayao Site—an early Late Pleistocene archaeological site in China. Results show multi-seasonal use in both the upper and lower layers of this site. Furthermore, attention is given to the method's future application in seasonality studies at Paleolithic archaeological sites in China.展开更多
Cementum,a thin layer of mineralized tissue covering tooth root surface,is recognized as the golden standard in periodontal regeneration.However,current efforts mainly focus on alveolar bone regeneration rather than c...Cementum,a thin layer of mineralized tissue covering tooth root surface,is recognized as the golden standard in periodontal regeneration.However,current efforts mainly focus on alveolar bone regeneration rather than cementum regeneration,and rarely take Porphyromonas gingivalis(Pg),the keystone pathogen responsible for periodontal tissue destruction,into consideration.Though M2 macrophage-derived exosomes(M2-EXO)show promise in tissue regeneration,the exosome-producing M2 macrophages are induced by exogenous cytokines with transitory and unstable effects,restricting the regeneration potential of M2-EXO.Here,exosomes derived from genetically engineered M2-like macrophages are constructed by silencing of casein kinase 2 interacting protein-1(Ckip-1),a versatile player involved in various biological processes.Ckip-1 silencing is proved to be an effective gene regulation strategy to obtain permanent M2-like macrophages with mineralization-promoting effect.Further,exosomes derived from Ckip-1-silenced macrophages(sh-Ckip-1-EXO)rescue Pg-suppressed cementoblast mineralization and cementogenesis.Mechanismly,sh-Ckip-1-EXO delivers Let-7f-5p targeting and silencing Ckip-1,a negative regulator also for cementum formation and cementoblast mineralization.More deeply,downregulation of Ckip-1 in cementoblasts by exosomal Let-7f-5p activates PGC-1α-dependent mitochondrial biogenesis.In all,this study provides a new strategy of genetically engineered M2-like macrophage-derived exosomes for cementum regeneration under Pg-dominated inflammation.展开更多
Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey＇s fibers ...Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey＇s fibers of the periodontal ligament （PDL）. However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 （Bmp2） in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 （PO）, followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2gene is removed from Sp7＋ （Osterix＋） cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC （Nfic）, periostin and α-SMA＋ cells. Third, there is a failure to produce vascular endothelial growth factor A （VEGF-A） in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOsp7-cre＇EGFe. Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOsp7-cre＇EGFe. These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.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 (in part) by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health
文摘The tooth root cementum is a thin, mineralized tissue covering the root dentin that is present primarily as acellular cementum on the cervical root and cellular cementum covering the apical root. While cementum shares many properties in common with bone and dentin, it is a unique mineralized tissue and acellular cementum is critical for attachment of the tooth to the surrounding periodontal ligament （PDL）. Resources for methodologies for hard tissues often overlook cementum and approaches that may be of value for studying this tissue. To address this issue, this report offers detailed methodology, as well as comparisons of several histological and immunohistochemical stains available for imaging the cementum-PDL complex by light microscopy. Notably, the infrequently used Alcian blue stain with nuclear fast red counterstain provided utility in imaging cementum in mouse, porcine and human teeth. While no truly unique extracellular matrix markers have been identified to differentiate cementum from the other hard tissues, immunohistochemistry for detection of bone sialoprotein （BSP）, osteopontin （OPN）, and dentin matrix protein 1 （DMP1） is a reliable approach for studying both acellular and cellular cementum and providing insight into developmental biology of these tissues. Histoloeical and immunohistochemical aooroaches Drovide insight on developmental biology of cementum.
基金supported by grant from Eng.A.B.Growth Factors and Bone Regeneration Research Chair and number #LR0003
文摘Periodontal regenerative techniques have been proposed; however, the outcomes remain debatable. The present investigation assessed the regenerated cementum following enamel matrix derivative application in dehiscence-type defects. Buccal osseous dehiscences were surgically created on the maxillary cuspid, and the second and fourth premolars in five female beagle dogs. The treatment group （n=15 sites） received the enamel matrix derived application, whereas the control groups （n=15） did not. The dogs were sacrificed 4 months following treatment and the specimens were histologically and histometrically examined. The newly formed cementum was uneven in thickness and mineralization, overlapped the old cementum and exhibited functional orientation, cementocyte lacunae and collagen fibril bundles. Most of the histological specimens showed the presence of a gap between the newly formed cementum and the underlying dentin. Control sites did not exhibit any cementum formation. The present study concluded that newly formed cementum is of cellular type and exhibits multiple characteristics.
基金Supported by the National Natural Science Foundation of China(No.30830108)the National Basic Research Program of China(No.2007CB936402)
文摘Determining the microstructure in human cementum might help us design new kinds of replacement materials for the treatment of teeth injury and disease. The authors characterized the nanostructures in the cementum of health human teeth via scanning electronic microscopy（SEM）. It was found that the acellular cementum is mainly composed of two kinds of nanostructures―inorganic nanoparticles and organic nanofibers. And the inorganic nanoparticles show a tendency to arrange along the organic nanofibers. Based on the micro-molding in capillary strategy, the distribution of organic component in acellular cementum was copied with UV curable resin. After removing the inorganic nanoparticles by acid etching, many isolated spindle shape nanopores were left in polymer, which su- ggested that the inorganic nanoparticles should have been isolated by the organic component in cementum, and should be oval or nanosheet in shape. We hope the present work could provide reference for the biomimetic preparation of tissue engineering materials, and help us design new types of tooth implant.
文摘In this paper, the elastic modulus measuring of human cementum is studied. The average value of the elastic modulus measured from 100 specimens is E = 2.398 +/- 0.455 GPa. The specimens were made from incisors, canines, bicuspids, and molars. The testing was done on type AG-10TA electronic-mechanical universal material testing machine. It was verified by mathematical statistics that the probability distribution of measured data obeys normal distribution. By the great difference in elastic moduli between cementum and dentin it is explained that 1. why more cementum grows at the root apexes; 2. the behavior of cementum must be taken into consideration when the stress analysis for teeth is carried out.
基金supported by the Key Research Program of the Chinese Academy of Sciences (Grant No.KZZD-EW-15)the Fundamental Project for Science and Technology of China (Grant No. 2014FY110300)the National Natural Science Foundation of China (Grant Nos. 41672024 & 41672023)
文摘Seasonality study of Paleolithic archaeological faunal assemblages is important for reconstructing modes of animal death and ancient hominin strategies for prey acquisition. The dental cementum of animal teeth records the season of an individual animal in which it died, providing the necessary evidence for determining any patterns in season of death. This article presents the procedure and preliminary results of the application of cementum incremental analysis to equid teeth, which comprise the dominant component of the fauna from the Xujiayao Site—an early Late Pleistocene archaeological site in China. Results show multi-seasonal use in both the upper and lower layers of this site. Furthermore, attention is given to the method's future application in seasonality studies at Paleolithic archaeological sites in China.
基金supported by the National Natural Science Foundation of China(No.82370967,No.82170963)。
文摘Cementum,a thin layer of mineralized tissue covering tooth root surface,is recognized as the golden standard in periodontal regeneration.However,current efforts mainly focus on alveolar bone regeneration rather than cementum regeneration,and rarely take Porphyromonas gingivalis(Pg),the keystone pathogen responsible for periodontal tissue destruction,into consideration.Though M2 macrophage-derived exosomes(M2-EXO)show promise in tissue regeneration,the exosome-producing M2 macrophages are induced by exogenous cytokines with transitory and unstable effects,restricting the regeneration potential of M2-EXO.Here,exosomes derived from genetically engineered M2-like macrophages are constructed by silencing of casein kinase 2 interacting protein-1(Ckip-1),a versatile player involved in various biological processes.Ckip-1 silencing is proved to be an effective gene regulation strategy to obtain permanent M2-like macrophages with mineralization-promoting effect.Further,exosomes derived from Ckip-1-silenced macrophages(sh-Ckip-1-EXO)rescue Pg-suppressed cementoblast mineralization and cementogenesis.Mechanismly,sh-Ckip-1-EXO delivers Let-7f-5p targeting and silencing Ckip-1,a negative regulator also for cementum formation and cementoblast mineralization.More deeply,downregulation of Ckip-1 in cementoblasts by exosomal Let-7f-5p activates PGC-1α-dependent mitochondrial biogenesis.In all,this study provides a new strategy of genetically engineered M2-like macrophage-derived exosomes for cementum regeneration under Pg-dominated inflammation.
基金partly supported by research grant funding:NIH-NIAMS R01- AR054616 (SEH), NIH-NIDCR T32-DE14318 (Rakian) and F32-DE018865 (Yang)supported by UTHSCSA, NIH-NCI P30-CA54174 (CTRC at UTHSCSA) and NIH-NIA P01-AG19316supported by Open Fund of State Key Laboratory of Oral Diseases, Sichuan University
文摘Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey＇s fibers of the periodontal ligament （PDL）. However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 （Bmp2） in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 （PO）, followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2gene is removed from Sp7＋ （Osterix＋） cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC （Nfic）, periostin and α-SMA＋ cells. Third, there is a failure to produce vascular endothelial growth factor A （VEGF-A） in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOsp7-cre＇EGFe. Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOsp7-cre＇EGFe. These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.
