scholarly journals Identification of Key Functional Motifs of Native Amelogenin Protein for Dental Enamel Remineralisation

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4214
Author(s):  
Shama S. M. Dissanayake ◽  
Manikandan Ekambaram ◽  
Kai Chun Li ◽  
Paul W. R. Harris ◽  
Margaret A. Brimble
Keyword(s):  
Dental Caries ◽  
Rational Design ◽  
Matrix Protein ◽  
Tooth Enamel ◽  
Critical Role ◽  
Dental Enamel ◽  
Tooth Decay ◽  
Structure Comparison ◽  
Physiological Importance

Dental caries or tooth decay is a preventable and multifactorial disease that affects billions of people globally and is a particular concern in younger populations. This decay arises from acid demineralisation of tooth enamel resulting in mineral loss from the subsurface. The remineralisation of early enamel carious lesions could prevent the cavitation of teeth. The enamel protein amelogenin constitutes 90% of the total enamel matrix protein in teeth and plays a key role in the biomineralisation of tooth enamel. The physiological importance of amelogenin has led to the investigation of the possible development of amelogenin-derived biomimetics against dental caries. We herein review the literature on amelogenin, its primary and secondary structure, comparison to related species, and its’ in vivo processing to bioactive peptide fragments. The key structural motifs of amelogenin that enable enamel remineralisation are discussed. The presence of several motifs in the amelogenin structure (such as polyproline, N- and C-terminal domains and C-terminal orientation) were shown to play a critical role in the formation of particle shape during remineralization. Understanding the function/structure relationships of amelogenin can aid in the rational design of synthetic polypeptides for biomineralisation, halting enamel loss and leading to improved therapies for tooth decay.

Mathematical Modeling of Caries Initiation and Progression Occurring in Dental Enamel

2013 ◽  
Vol 592-593 ◽  
pp. 362-365 ◽  
Author(s):  
Roman I. Izyumov ◽  
Sergey V. Rusakov ◽  
Andrew L. Zuev ◽  
Olga S. Gileva ◽  
Maria A. Muraveva
Keyword(s):  
Dental Caries ◽  
Tooth Enamel ◽  
Subsurface Layer ◽  
Dental Enamel ◽  
Modern Method ◽  
Tooth Decay ◽  
Caries Treatment ◽  
Proposed Model ◽  
Dental Hard Tissues ◽  
Damaged Zone

The paper is concerned with the investigation of dental caries treatment by the modern method based on the application of special composite material that can diffuse into the damaged zone, harden by light and prevent tooth decay. Carious disease was modeled as a diffusion process of acid penetration from the oral cavity into the tooth enamel with further dissolution of dental hard tissues in the subsurface layer of enamel. The model of dental caries was mathematically formulated. The solution was obtained by a numerical method using MATLAB. It is shown that the proposed model adequately describes the properties of the examined dental system.

scholarly journals Glycoprotein N-linked glycans play a critical role in arenavirus pathogenicity

2021 ◽  
Vol 17 (3) ◽  
pp. e1009356
Author(s):  
Takaaki Koma ◽  
Cheng Huang ◽  
Adrian Coscia ◽  
Steven Hallam ◽  
John T. Manning ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Rational Design ◽  
Critical Role ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Wild Type ◽  
Virus Growth ◽  
Glycosylation Sites

Several arenaviruses cause hemorrhagic fevers in humans with high case fatality rates. A vaccine named Candid#1 is available only against Junin virus (JUNV) in Argentina. Specific N-linked glycans on the arenavirus surface glycoprotein (GP) mask important epitopes and help the virus evade antibody responses. However the role of GPC glycans in arenavirus pathogenicity is largely unclear. In a lethal animal model of hemorrhagic fever-causing Machupo virus (MACV) infection, we found that a chimeric MACV with the ectodomain of GPC from Candid#1 vaccine was partially attenuated. Interestingly, mutations resulting in acquisition of N-linked glycans at GPC N83 and N166 frequently occurred in late stages of the infection. These glycosylation sites are conserved in the GPC of wild-type MACV, indicating that this is a phenotypic reversion for the chimeric MACV to gain those glycans crucial for infection in vivo. Further studies indicated that the GPC mutant viruses with additional glycans became more resistant to neutralizing antibodies and more virulent in animals. On the other hand, disruption of these glycosylation sites on wild-type MACV GPC rendered the virus substantially attenuated in vivo and also more susceptible to antibody neutralization, while loss of these glycans did not affect virus growth in cultured cells. We also found that MACV lacking specific GPC glycans elicited higher levels of neutralizing antibodies against wild-type MACV. Our findings revealed the critical role of specific glycans on GPC in arenavirus pathogenicity and have important implications for rational design of vaccines against this group of hemorrhagic fever-causing viruses.

Lemon myrtle extract inhibits lactate production by Streptococcus mutans

2021 ◽  
Vol 85 (10) ◽  
pp. 2185-2190
Author(s):  
Yukinori Yabuta ◽  
Yui Sato ◽  
Arisu Miki ◽  
Ryuta Nagata ◽  
Tomohiro Bito ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Dental Caries ◽  
Oral Cavity ◽  
Streptococcus Mutans ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Tooth Enamel ◽  
Lactate Production ◽  
Tooth Decay ◽  
Lactate Dehydrogenase Activity

ABSTRACT Backhousia citriodora (lemon myrtle) extract has been found to inhibit glucansucrase activity, which plays an important role in biofilm formation by Streptococcus mutans. In addition to glucansucrase, various virulence factors in S. mutans are involved in the initiation of caries. Lactate produced by S. mutans demineralizes the tooth enamel. This study investigated whether lemon myrtle extract can inhibit S. mutans lactate production. Lemon myrtle extract reduced the glycolytic pH drop in S. mutans culture and inhibited lactate production by at least 46%. Ellagic acid, quercetin, hesperetin, and myricetin, major polyphenols in lemon myrtle, reduced the glycolytic pH drop and lactate production, but not lactate dehydrogenase activity. Furthermore, these polyphenols reduced the viable S. mutans cell count. Thus, lemon myrtle extracts may inhibit S. mutans-mediated acidification of the oral cavity, thereby preventing dental caries and tooth decay.

Structure-Property Correlation in Genetically-Engineered Mouse Enamel

2001 ◽  
Vol 7 (S2) ◽  
pp. 992-993
Author(s):  
Hanson Fong ◽  
Daniel Heidel ◽  
Mehmet Sarikaya ◽  
Michael Paine ◽  
Wen Lou ◽  
...  
Keyword(s):  
Self Assembly ◽  
Matrix Protein ◽  
Dental Enamel ◽  
Genetically Engineered ◽  
Structure Property ◽  
Biomineralization Process ◽  
Enamel Epithelium ◽  
Assembly Behavior

Dental enamel is the most durable bioceramics produced by a vertebrate as it is designed to perform masticatory functions throughout its lifetime. The understanding of the mechanism of enamel formation and effects of proteins during the biomineralization process are fundamental issues, essential for both potential enamel regeneration and as a base for synthesis, via self-assembly, of biomimetic composites.The biomineralization process of enamel is carried out by ameloblast cells that line the inner enamel epithelium and secrete an extracellular protein matrix onto a mineralized dentin surface at the dentin-enamel junction (DEJ). A major matrix protein, amelogenin, is believed to regulate the mineralization of hydroxyapatite (HAP) in the enamel tissue. It has been shown to undergo self-assembly in vitro and in vivo to form nanospheres of ∼20nm in diameter. Previous TEM studies have shown that the nanospheres align along the length (c-axis) of hydroxyapatite (HA) crystals. There are two domains, namely A (residues 1-42) and B (residues 157-173), that control the self-assembly behavior of the nanospheres.

scholarly journals Immunological Aspects of Recombinant Adeno-Associated Virus Delivery to the Mammalian Brain

2002 ◽  
Vol 76 (16) ◽  
pp. 8446-8454 ◽  
Author(s):  
Mihail Y. Mastakov ◽  
Kristin Baer ◽  
C. Wymond Symes ◽  
Claudia B. Leichtlein ◽  
Robert M. Kotin ◽  
...  
Keyword(s):  
Rational Design ◽  
Critical Role ◽  
Repeated Administration ◽  
Mammalian Brain ◽  
Adeno Associated Virus ◽  
Genomic Studies ◽  
The Central Nervous System ◽  
Genetic Sequences ◽  
Virus Delivery

ABSTRACT Recombinant adeno-associated viruses (rAAV) are highly efficient vectors for gene delivery into the central nervous system (CNS). However, host inflammatory and immune responses may play a critical role in limiting the use of rAAV vectors for gene therapy and functional genomic studies in vivo. Here, we evaluated the effect of repeated injections of five rAAV vectors expressing different genetic sequences (coding or noncoding) in a range of combinations into the rat brain. Specifically, we wished to determine whether a specific immune or inflammatory response appeared in response to the vector and/or the transgene protein after repeated injections under conditions of mannitol coinjection. We show that readministration of the same rAAV to the CNS is possible if the interval between the first and second injection is more than 4 weeks. Furthermore, our data demonstrate that rAAV vectors carrying different genetic sequences can be administered at intervals of 2 weeks. Our data therefore suggest that the AAV capsid structure is altered by the vector genetic sequence, such that secondary structures of the single-stranded genome have an impact on the antigenicity of the virus. This study provides guidelines for more rational design of gene transfer studies in the rodent brain and, in addition, suggests the use of repeated administration of rAAV as a viable form of therapy for the treatment of chronic diseases.

scholarly journals Genetic perturbation of the putative cytoplasmic membrane-proximal salt bridge aberrantly activates α4 integrins

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 5007-5015 ◽  
Author(s):  
Yoichi Imai ◽  
Eun Jeong Park ◽  
Dan Peer ◽  
António Peixoto ◽  
Guiying Cheng ◽  
...  
Keyword(s):  
Cell Migration ◽  
Conformational Changes ◽  
Solution Structure ◽  
Germ Line ◽  
Critical Role ◽  
Salt Bridge ◽  
Physiological Importance ◽  
Endothelial Monolayers ◽  
Integrin Regulation

Abstract α4 integrins play a pivotal role in leukocyte migration and tissue-specific homing. The ability of integrins to bind ligand is dynamically regulated by activation-dependent conformational changes triggered in the cytoplasmic domain. An NMR solution structure defined a putative membrane-proximal salt bridge between the αIIbβ3 integrin cytoplasmic tails, which restrains integrins in their low-affinity state. However, the physiological importance of this salt bridge in α4 integrin regulation remains to be elucidated. To address this question, we disrupted the salt bridge in murine germ line by mutating the conserved cytoplasmic arginine RGFFKR in α4 integrins. In lymphocytes from knock-in mice (α4-R/AGFFKR), α4β1 and α4β7 integrins exhibited constitutively up-regulated ligand binding. However, transmigration of these cells across VCAM-1 and MAdCAM-1 substrates, or across endothelial monolayers, was reduced. Perturbed detachment of the tail appeared to cause the reduced cell migration of α4-R/AGFFKR lymphocytes. In vivo, α4-R/AGFFKR cells exhibited increased firm adhesion to Peyer patch venules but reduced homing to the gut. Our results demonstrate that the membrane-proximal salt bridge plays a critical role in supporting proper α4 integrin adhesive dynamics. Loss of this interaction destabilizes the nonadhesive conformation, and thereby perturbs the properly balanced cycles of adhesion and deadhesion required for efficient cell migration.

FLUORIDE AS A NUTRIEN

PEDIATRICS ◽  
1972 ◽  
Vol 49 (3) ◽  
pp. 456-460
Author(s):  
L. J. Filer ◽  
Lewis A. Barness ◽  
Richard B. Goldbloom ◽  
Malcolm A. Holliday ◽  
Robert W. Miller ◽  
...  
Keyword(s):  
Drinking Water ◽  
Dental Caries ◽  
Tooth Enamel ◽  
Dental Fluorosis ◽  
Normal Component ◽  
Fluoride Content ◽  
Water Supplies ◽  
Calcified Tissues

The association of mottled enamel and dental fluorosis with community drinking water was detected before 1920 and was specifically related to the fluoride content of the water when Churchill, in 1931,1 was able to measure trace amounts of fluoride in drinking water. Also, in areas with communal water supplies naturally contaming increased amounts of fluoride, the occurrence of dental caries was lower than that seen in the general population.2 These observations and subsequent studies3 led to the practice of adding fluoride to communal waters, with a consequent significant reduclion in the incidence of dental caries. Nearly 90 million persons in 7,500 communities4 use water supplies containing an amount of fluoride effective in reducing the dental caries rate. Fluoride is present in the customary diet and in most potable water sources in amounts that vary from 0.1 to 0.5 parts per million (ppm).5 The average dietary intake of fluoride is approximately 0.5 mg daily from these two sources. In the temperate zone, fluoridated community water supplies are increased in fluoride content to a level of 1.0 ppm, thus providing, on the average, a total fluoride ingestion of 1.5 mg per day. A lesser level of fluoridation may be sufficient in warmer climates conducive to a higher water consumption. Fluoride is regarded as an essential nutrient6 and it is now well known to be effective in the maintenance of a tooth enamel that is more resistant to decay. Fluoride is a normal component of tooth enamel and bone. Studies in vivo and in vitro demonstrate that the calcified tissues of both enamel and bone are made up of a combination of hydroxy- and fluor-apatites of varying composition, depending on the abundance of fluoride at the site of formation.

scholarly journals Polyphenols of Honeybee Origin with Applications in Dental Medicine

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 856
Author(s):  
Carmen Curuțiu ◽  
Lia Mara Dițu ◽  
Alexandru Mihai Grumezescu ◽  
Alina Maria Holban
Keyword(s):  
Dental Caries ◽  
Dental Enamel ◽  
Plaque Formation ◽  
Oral Diseases ◽  
Biological Mechanisms ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Oral Conditions

Honeybee products are a great source of polyphenols with recognized applications in dental medicine. Although their biological mechanisms in oral diseases are not fully understood, numerous in vitro, in vivo and clinical studies have reported promising results in the prevention and treatment of oral diseases. Bioactivities, such as antibacterial, antiviral, antiparasite, anticancer, anti-inflammatory and anti-oxidant properties, recommend their future study in order to develop efficient alternatives in the management of widespread oral conditions, such as dental caries and periodontitis. The most investigated mechanisms of polyphenols in oral health rely on their ability to strengthen the dental enamel, decrease the development of dental plaque formation, inhibit the progression of dental caries and development of dental pathogens and show anti-inflammatory properties. These features recommend them as useful honeybee candidates in the management of emerging oral diseases.

In vivo protective effects of upper zone of growth plate and cartilage matrix associated protein against cartilage degeneration in a monosodium iodoacetate induced osteoarthritis model

2020 ◽  
Vol 98 (11) ◽  
pp. 763-770
Author(s):  
Hamza Malik Okuyan ◽  
Menderes Yusuf Terzi ◽  
İhsan Karaboğa ◽  
Serdar Doğan ◽  
Aydıner Kalacı
Keyword(s):  
Growth Plate ◽  
Matrix Protein ◽  
Critical Role ◽  
Cartilage Degeneration ◽  
Cartilage Matrix ◽  
Bone Morphogenetic Protein 2 ◽  
Monosodium Iodoacetate ◽  
And Cartilage

Osteoarthritis (OA) is a degenerative disease affecting the majority of over 65 year old people and characterized by cartilage degeneration, subchondral abnormal changes, and inflammation. Despite the enormous socioeconomic burden caused by OA, currently, there is no effective therapy against it. Upper zone of growth plate and cartilage matrix associated protein (UCMA) is a vitamin K dependent protein and has a critical role in pathophysiological conditions associated with bone and cartilage. However, there is no research on the protective role of intra-articular UCMA treatment in OA pathogenesis. Therefore, we aimed to investigate the potential therapeutic role of UCMA in an in vivo model of OA. We report for the first time that intra-articular UCMA injection ameliorated cartilage degeneration in a monosodium iodoacetate induced OA rat model. Furthermore, the OA-induced activation of nuclear factor kappa B and bone morphogenetic protein 2 signals was attenuated by UCMA. Our results indicated that UCMA decreased cartilage oligomeric matrix protein levels but did not affect interleukin 6, total antioxidant status, and total oxidant status levels in the serum. In conclusion, UCMA exhibited a therapeutic potential in the treatment of OA. This protective effect of UCMA is possibly achieved by reducing the aggrecanase activity and the production of inflammatory cytokines.

scholarly journals Amelogenin phosphorylation regulates tooth enamel formation by stabilizing a transient amorphous mineral precursor

2020 ◽  
Vol 295 (7) ◽  
pp. 1943-1959 ◽  
Author(s):  
Nah-Young Shin ◽  
Hajime Yamazaki ◽  
Elia Beniash ◽  
Xu Yang ◽  
Seth S. Margolis ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Surface Defects ◽  
Tooth Enamel ◽  
Phosphorylation Site ◽  
Dental Enamel ◽  
Crystal Formation ◽  
Enamel Formation ◽  
Enamel Matrix Protein ◽  
And Function

Dental enamel comprises interwoven arrays of extremely long and narrow crystals of carbonated hydroxyapatite called enamel rods. Amelogenin (AMELX) is the predominant extracellular enamel matrix protein and plays an essential role in enamel formation (amelogenesis). Previously, we have demonstrated that full-length AMELX forms higher-order supramolecular assemblies that regulate ordered mineralization in vitro, as observed in enamel rods. Phosphorylation of the sole AMELX phosphorylation site (Ser-16) in vitro greatly enhances its capacity to stabilize amorphous calcium phosphate (ACP), the first mineral phase formed in developing enamel, and prevents apatitic crystal formation. To test our hypothesis that AMELX phosphorylation is critical for amelogenesis, we generated and characterized a hemizygous knockin (KI) mouse model with a phosphorylation-defective Ser-16 to Ala-16 substitution in AMELX. Using EM analysis, we demonstrate that in the absence of phosphorylated AMELX, KI enamel lacks enamel rods, the hallmark component of mammalian enamel, and, unlike WT enamel, appears to be composed of less organized arrays of shorter crystals oriented normal to the dentinoenamel junction. KI enamel also exhibited hypoplasia and numerous surface defects, whereas heterozygous enamel displayed highly variable mosaic structures with both KI and WT features. Importantly, ACP-to-apatitic crystal transformation occurred significantly faster in KI enamel. Secretory KI ameloblasts also lacked Tomes' processes, consistent with the absence of enamel rods, and underwent progressive cell pathology throughout enamel development. In conclusion, AMELX phosphorylation plays critical mechanistic roles in regulating ACP-phase transformation and enamel crystal growth, and in maintaining ameloblast integrity and function during amelogenesis.

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