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1.
Sci Rep ; 12(1): 6172, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35418659

RESUMO

Odontodes, i.e., teeth and tooth-like structures, consist of a pulp cavity and dentin covered by a mineralized cap. These structures first appeared on the outer surface of vertebrate ancestors and were repeatedly lost and gained across vertebrate clades; yet, the underlying genetic mechanisms and trajectories of this recurrent evolution remain long-standing mysteries. Here, we established suckermouth armored catfish (Ancistrus sp.; Loricariidae), which have reacquired dermal odontodes (dermal denticles) all over most of their body surface, as an experimental model animal amenable to genetic manipulation for studying odontode development. Our histological analysis showed that suckermouth armored catfish develop dermal denticles through the previously defined odontode developmental stages. De novo transcriptomic profiling identified the conserved odontode genetic regulatory network (oGRN) as well as expression of paired like homeodomain 2 (pitx2), previously known as an early regulator of oGRN in teeth but not in other dermal odontodes, in developing dermal denticles. The early onset of pitx2 expression in cranial dermal denticle placodes implies its function as one of the inducing factors of the cranial dermal denticles. By comprehensively identifying the genetic program for dermal odontode development in suckermouth armored catfish, this work illuminates how dermal odontodes might have evolved and diverged in distinct teleost lineages via redeployment of oGRN.


Assuntos
Peixes-Gato , Calcificações da Polpa Dentária , Dente , Animais , Evolução Biológica , Peixes-Gato/genética , Redes Reguladoras de Genes , Dente/metabolismo
2.
Sci Rep ; 12(1): 2820, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35181734

RESUMO

As the hardest tissue in the human body, tooth enamel formation is a highly regulated process involving several stages of differentiation and key regulatory genes. One such gene, tryptophan-aspartate repeat domain 72 (WDR72), has been found to cause a tooth enamel defect when deleted or mutated, resulting in a condition called amelogenesis imperfecta. Unlike the canonical genes regulating tooth development, WDR72 remains intracellularly and is not secreted to the enamel matrix space to regulate mineralization, and is found in other major organs of the body, namely the kidney, brain, liver, and heart. To date, a link between intracellular vesicle transport and enamel mineralization has been suggested, however identification of the mechanistic regulators has yet to be elucidated, in part due to the limitations associated with studying highly differentiated ameloblast cells. Here we show compelling evidence that WDR72 regulates endocytosis of proteins, both in vivo and in a novel in vitro ameloblast cell line. We elucidate WDR72's function to be independent of intracellular vesicle acidification while still leading to defective enamel matrix pH extracellularly. We identify a vesicle function associated with microtubule assembly and propose that WDR72 directs microtubule assembly necessary for membrane mobilization and subsequent vesicle transport. Understanding WDR72 function provides a mechanistic basis for determining physiologic and pathologic tissue mineralization.


Assuntos
Ameloblastos/metabolismo , Calcificação Fisiológica/genética , Esmalte Dentário/crescimento & desenvolvimento , Dente/crescimento & desenvolvimento , Amelogênese Imperfeita/genética , Amelogênese Imperfeita/patologia , Encéfalo/metabolismo , Diferenciação Celular/genética , Esmalte Dentário/metabolismo , Endocitose/genética , Humanos , Rim/metabolismo , Fígado/metabolismo , Microtúbulos/genética , Miocárdio/metabolismo , Dente/metabolismo
3.
Int J Mol Sci ; 23(3)2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35163584

RESUMO

Application of mesenchymal stem cells (MSC) in regenerative therapeutic procedures is becoming an increasingly important topic in medicine. Since the first isolation of dental tissue-derived MSC, there has been an intense investigation on the characteristics and potentials of these cells in regenerative dentistry. Their multidifferentiation potential, self-renewal capacity, and easy accessibility give them a key role in stem cell-based therapy. So far, several different dental stem cell types have been discovered and their potential usage is found in most of the major dental medicine branches. These cells are also researched in multiple fields of medicine for the treatment of degenerative and inflammatory diseases. In this review, we summarized dental MSC sources and analyzed their treatment modalities with particular emphasis on temporomandibular joint osteoarthritis (TMJ OA).


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Osteoartrite , Medicina Regenerativa , Transtornos da Articulação Temporomandibular , Articulação Temporomandibular/metabolismo , Dente/metabolismo , Humanos , Osteoartrite/metabolismo , Osteoartrite/terapia , Transtornos da Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/terapia
4.
Adv Sci (Weinh) ; 9(4): e2103839, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34894103

RESUMO

Mitochondrial dysfunction in tissue-specific mesenchymal stem cells (MSCs) plays a critical role in cell fate and the morbidity of chronic inflammation-associated bone diseases, such as periodontitis and osteoarthritis. However, there is still no effective method to cure chronic inflammation-associated bone diseases by physiologically restoring the function of mitochondria and MSCs. Herein, it is first found that chronic inflammation leads to excess Ca2+ transfer from the endoplasmic reticulum to mitochondria, which causes mitochondrial calcium overload and further damage to mitochondria. Furthermore, damaged mitochondria continuously accumulate in MSCs due to the inhibition of mitophagy by activating the Wnt/ß-catenin pathway under chronic inflammatory conditions, impairing the differentiation of MSCs. Based on the mechanistic discovery, intracellular microenvironment (esterase and low pH)-responsive nanoparticles are fabricated to capture Ca2+ around mitochondria in MSCs to regulate MSC mitochondrial calcium flux against mitochondrial dysfunction. Furthermore, the same nanoparticles are able to deliver siRNA to MSCs to inhibit the Wnt/ß-catenin pathway and regulate mitophagy of the originally dysfunctional mitochondria. These precision-engineered nanoparticles, referred to as "nanorepairers," physiologically restore the function of mitochondria and MSCs, resulting in effective therapy for periodontitis and osteoarthritis. The concept can potentially be expanded to the treatment of other diseases via mitochondrial quality control intervention.


Assuntos
Inflamação/metabolismo , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias/metabolismo , Nanopartículas/metabolismo , Animais , Medula Óssea/metabolismo , Diferenciação Celular , China , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoartrite do Joelho/metabolismo , Periodontite/metabolismo , Ratos , Ratos Sprague-Dawley , Dente/metabolismo , Adulto Jovem
5.
Int J Mol Sci ; 22(23)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34884488

RESUMO

In dental pulp, diverse types of cells mediate the dental pulp immunity in a highly complex and dynamic manner. Yet, 3D spatiotemporal changes of various pulpal immune cells dynamically reacting against foreign pathogens during immune response have not been well characterized. It is partly due to the technical difficulty in detailed 3D comprehensive cellular-level observation of dental pulp in whole intact tooth beyond the conventional histological analysis using thin tooth slices. In this work, we validated the optical clearing technique based on modified Murray's clear as a valuable tool for a comprehensive cellular-level analysis of dental pulp. Utilizing the optical clearing, we successfully achieved a 3D visualization of CD11c+ dendritic cells in the dentin-pulp complex of a whole intact murine tooth. Notably, a small population of unique CD11c+ dendritic cells extending long cytoplasmic processes into the dentinal tubule while located at the dentin-pulp interface like odontoblasts were clearly visualized. 3D visualization of whole murine tooth enabled a reliable observation of these rarely existing cells with a total number less than a couple of tens in one tooth. These CD11c+ dendritic cells with processes in the dentinal tubule were significantly increased in the dental pulpitis model induced by mechanical and chemical irritation. Additionally, the 3D visualization revealed a distinct spatial 3D arrangement of pulpal CD11c+ cells in the pulp into a front-line barrier-like formation in the pulp within 12 h after the irritation. Collectively, these observations demonstrated the unique capability of optical clearing-based comprehensive 3D cellular-level visualization of the whole tooth as an efficient method to analyze 3D spatiotemporal changes of various pulpal cells in normal and pathological conditions.


Assuntos
Antígeno CD11c/metabolismo , Células Dendríticas/imunologia , Polpa Dentária/imunologia , Imageamento Tridimensional/métodos , Pulpite/imunologia , Dente/imunologia , Animais , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Polpa Dentária/metabolismo , Polpa Dentária/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pulpite/metabolismo , Pulpite/patologia , Dente/metabolismo , Dente/patologia
6.
Int J Mol Sci ; 22(23)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34884758

RESUMO

Biomineralization is the process by which organisms produce hard inorganic matter from soft tissues with outstanding control of mineral deposition in time and space. For this purpose, organisms deploy a sophisticated "toolkit" that has resulted in significant evolutionary innovations, for which calcium phosphate (CaP) is the biomineral selected for the skeleton of vertebrates. While CaP mineral formation in aqueous media can be investigated by studying thermodynamics and kinetics of phase transitions in supersaturated solutions, biogenic mineralization requires coping with the inherent complexity of biological systems. This mainly includes compartmentalization and homeostatic processes used by organisms to regulate key physiological factors, including temperature, pH and ion concentration. A detailed analysis of the literature shows the emergence of two main views describing the mechanism of CaP biomineralization. The first one, more dedicated to the study of in vivo systems and supported by researchers in physiology, often involves matrix vesicles (MVs). The second one, more investigated by the physicochemistry community, involves collagen intrafibrillar mineralization particularly through in vitro acellular models. Herein, we show that there is an obvious need in the biological systems to control both where and when the mineral forms through an in-depth survey of the mechanism of CaP mineralization. This necessity could gather both communities of physiologists and physicochemists under a common interest for an enzymatic approach to better describe CaP biomineralization. Both homogeneous and heterogeneous enzymatic catalyses are conceivable for these systems, and a few preliminary promising results on CaP mineralization for both types of enzymatic catalysis are reported in this work. Through them, we aim to describe the relevance of our point of view and the likely findings that could be obtained when adding an enzymatic approach to the already rich and creative research field dealing with CaP mineralization. This complementary approach could lead to a better understanding of the biomineralization mechanism and inspire the biomimetic design of new materials.


Assuntos
Biomineralização/fisiologia , Fosfatos de Cálcio/química , Fosfatos de Cálcio/metabolismo , Fosfatase Alcalina/química , Fosfatase Alcalina/metabolismo , Animais , Biocatálise , Evolução Biológica , Osso e Ossos/metabolismo , Cartilagem/metabolismo , Fenômenos Químicos , Colágeno/química , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Técnicas In Vitro , Modelos Biológicos , Filogenia , Dente/metabolismo
7.
J Mater Sci Mater Med ; 32(12): 150, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34874480

RESUMO

OBJECTIVES: The objective of the present work was to evaluate the ultrasonic agitation, time and vehicle (propylene glycol or distilled water) on the antimicrobial potential and penetrability of calcium hydroxide pastes on infected dentin by means of Confocal Laser Scanning Microscopy (CLSM) and microbiological culture (MC). MATERIALS AND METHODS: Dentin specimens were infected with Enterococcus faecalis using a new contamination protocol of 5 days. The specimens were divided into eight groups and dressed with the pastes for 7 or 15 days: G1) calcium hydroxide (CH) + propylene glycol (prop)/7 days (d), G2) CH + prop/7d + ultrasonic agitation (U), G3) CH + distilled water (dw)/7d, G4) CH + dw/7d + U, G5) CH + prop/15d, G6) CH + prop/15d + U, G7) CH + dw/15d, G8) CH + dw/15d + U. The ultrasonic activation was made for 1 min in both directions with a plain point insert. After medications removal, the images obtained by CLSM showed the viable (green) and dead (red) bacteria with Live and Dead dye. By the MC, the dentinal wall debris obtained by burs were collected for colony counts. For the penetration test, the Rodamine B dye was added to the CH pastes and analyzed by CLSM. RESULTS: The 7 and 15-days CH + prop+U pastes performed better antimicrobial efficacy, followed by the CH + dw+U/15d paste. CONCLUSIONS: All pastes demonstrated better penetration and antimicrobial activity against E. faecalis when agitated with ultrasound, even in periods of up to seven days. The propylene glycol vehicle showed better results. CLINICAL RELEVANCE: Agitation of the dressing that remains for less time inside the root canal can optimize the decontamination of endodontic treatment.


Assuntos
Hidróxido de Cálcio/farmacologia , Dente , Terapia por Ultrassom/efeitos adversos , Animais , Anti-Infecciosos/farmacologia , Hidróxido de Cálcio/farmacocinética , Bovinos , Cimentos Dentários/farmacocinética , Cimentos Dentários/farmacologia , Cavidade Pulpar/efeitos dos fármacos , Cavidade Pulpar/microbiologia , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Materiais Restauradores do Canal Radicular/farmacocinética , Materiais Restauradores do Canal Radicular/farmacologia , Irrigantes do Canal Radicular/farmacocinética , Fatores de Tempo , Dente/efeitos dos fármacos , Dente/metabolismo , Dente/microbiologia , Permeabilidade Dentária/efeitos dos fármacos , Ultrassom/métodos
8.
Biosci Rep ; 41(11)2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34724040

RESUMO

Lysine methyltransferase 2D (KMT2D), as one of the key histone methyltransferases responsible for histone 3 lysine 4 methylation (H3K4me), has been proved to be the main pathogenic gene of Kabuki syndrome disease. Kabuki patients with KMT2D mutation frequently present various dental abnormalities, including abnormal tooth number and crown morphology. However, the exact function of KMT2D in tooth development remains unclear. In this report, we systematically elucidate the expression pattern of KMT2D in early tooth development and outline the molecular mechanism of KMT2D in dental epithelial cell line. KMT2D and H3K4me mainly expressed in enamel organ and Kmt2d knockdown led to the reduction in cell proliferation activity and cell cycling activity in dental epithelial cell line (LS8). RNA-sequencing (RNA-seq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis screened out several important pathways affected by Kmt2d knockdown including Wnt signaling. Consistently, Top/Fop assay confirmed the reduction in Wnt signaling activity in Kmt2d knockdown cells. Nuclear translocation of ß-catenin was significantly reduced by Kmt2d knockdown, while lithium chloride (LiCl) partially reversed this phenomenon. Moreover, LiCl partially reversed the decrease in cell proliferation activity and G1 arrest, and the down-regulation of Wnt-related genes in Kmt2d knockdown cells. In summary, the present study uncovered a pivotal role of histone methyltransferase KMT2D in dental epithelium proliferation and cell cycle homeostasis partially through regulating Wnt/ß-catenin signaling. The findings are important for understanding the role of KMT2D and histone methylation in tooth development.


Assuntos
Células Epiteliais/metabolismo , Histona-Lisina N-Metiltransferase/deficiência , Histona-Lisina N-Metiltransferase/genética , Proteína de Leucina Linfoide-Mieloide/deficiência , Proteína de Leucina Linfoide-Mieloide/genética , Dente/metabolismo , Via de Sinalização Wnt/genética , Animais , Proteína Quinase CDC2/metabolismo , Ciclo Celular/genética , Linhagem Celular , Proliferação de Células/genética , Ciclina D1/metabolismo , Células Epiteliais/citologia , Histonas/metabolismo , Cloreto de Lítio/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Dente Molar/metabolismo , Dente/citologia , Via de Sinalização Wnt/efeitos dos fármacos
9.
Sci Rep ; 11(1): 20653, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34667213

RESUMO

Non-syndromic inherited defects of tooth dentin are caused by two classes of dominant negative/gain-of-function mutations in dentin sialophosphoprotein (DSPP): 5' mutations affecting an N-terminal targeting sequence and 3' mutations that shift translation into the - 1 reading frame. DSPP defects cause an overlapping spectrum of phenotypes classified as dentin dysplasia type II and dentinogenesis imperfecta types II and III. Using CRISPR/Cas9, we generated a Dspp-1fs mouse model by introducing a FLAG-tag followed by a single nucleotide deletion that translated 493 extraneous amino acids before termination. Developing incisors and/or molars from this mouse and a DsppP19L mouse were characterized by morphological assessment, bSEM, nanohardness testing, histological analysis, in situ hybridization and immunohistochemistry. DsppP19L dentin contained dentinal tubules but grew slowly and was softer and less mineralized than the wild-type. DsppP19L incisor enamel was softer than normal, while molar enamel showed reduced rod/interrod definition. Dspp-1fs dentin formation was analogous to reparative dentin: it lacked dentinal tubules, contained cellular debris, and was significantly softer and thinner than Dspp+/+ and DsppP19L dentin. The Dspp-1fs incisor enamel appeared normal and was comparable to the wild-type in hardness. We conclude that 5' and 3' Dspp mutations cause dental malformations through different pathological mechanisms and can be regarded as distinct disorders.


Assuntos
Dentinogênese Imperfeita/genética , Proteínas da Matriz Extracelular/genética , Fosfoproteínas/genética , Sialoglicoproteínas/genética , Animais , Esmalte Dentário/metabolismo , Dentina/metabolismo , Dentinogênese Imperfeita/metabolismo , Dentinogênese Imperfeita/fisiopatologia , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/metabolismo , Feminino , Mutação da Fase de Leitura/genética , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Fenótipo , Fosfoproteínas/metabolismo , Sialoglicoproteínas/metabolismo , Dente/metabolismo
10.
ACS Appl Mater Interfaces ; 13(39): 46247-46259, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34570460

RESUMO

Engineering highly sensitive nanomaterials to monitor spatiotemporal pH changes has rather broad applications in studying various biological systems. Intraoral/biofilm-tooth pH is the single parameter that has demonstrated accurate assessment of dental caries risk, reflecting the summative integrated outcome of the complicated interactions between three etiological factors, namely, microorganisms/biofilm, diet/carbohydrates, and tooth/saliva/host. However, there is little to no technology/system capable of accurately probing simultaneously both the micro-pH profiles in dentin tissues and acidogenic oral biofilms and examining the pathophysiologic acid attacks with high spatial/temporal resolution. Therefore, a highly sensitive pH-responsive hybrid nanoparticle (pH-NP) is developed and coupled with an ex vivo tooth-biofilm caries model to simulate and study the key cariogenic determinants/steps. The pH-NP emits two distinct fluorescences with mutually inversely proportional intensities that vary accordingly to the proximity pH and with a ratiometric output sensitivity of 13.4-fold across a broad clinically relevant pH range of 3.0-8.0. Using [H+], in addition to pH, to calculate the "area-under-curve" corroborates the "minimum-pH" in semiquantifying the demineralizing potential in each biofilm-dentin zones/depth. The data mechanistically elucidates a two-pronged cariogenic effect of a popular-acidic-sweet-drink, in inundating the biofilm/tooth-system with H+ ions from both the drink and the metabolic byproducts of the biofilm.


Assuntos
Microambiente Celular/fisiologia , Cárie Dentária/metabolismo , Dentina/metabolismo , Corantes Fluorescentes/química , Nanopartículas/química , Bebidas/efeitos adversos , Biofilmes , Dentina/diagnóstico por imagem , Humanos , Concentração de Íons de Hidrogênio , Azul de Metileno/química , Coroa de Proteína/química , Dióxido de Silício/química , Streptococcus mutans/metabolismo , Streptococcus mutans/fisiologia , Dente/metabolismo
11.
Dev Dyn ; 250(12): 1796-1809, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34091971

RESUMO

BACKGROUND: Hand genes are required for the development of the vertebrate jaw, heart, peripheral nervous system, limb, gut, placenta, and decidua. Two Hand paralogues, Hand1 and Hand2, are present in most vertebrates, where they mediate different functions yet overlap in expression. In ray-finned fishes, Hand gene expression and function is only known for the zebrafish, which represents the rare condition of having a single Hand gene, hand2. Here we describe the developmental expression of hand1 and hand2 in the cichlid Copadichromis azureus. RESULTS: hand1 and hand2 are expressed in the cichlid heart, paired fins, pharyngeal arches, peripheral nervous system, gut, and lateral plate mesoderm with different degrees of overlap. CONCLUSIONS: Hand gene expression in the gut, peripheral nervous system, and pharyngeal arches may have already been fixed in the lobe- and ray-finned fish common ancestor. In other embryonic regions, such as paired appendages, hand2 expression was fixed, while hand1 expression diverged in lobe- and ray-finned fish lineages. In the lateral plate mesoderm and arch associated catecholaminergic cells, hand1 and hand2 swapped expression between divergent lineages. Distinct expression of cichlid hand1 and hand2 in the epicardium and myocardium of the developing heart may represent the ancestral pattern for bony fishes.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Ciclídeos/embriologia , Desenvolvimento Embrionário/genética , Nadadeiras de Animais/embriologia , Nadadeiras de Animais/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Região Branquial/embriologia , Região Branquial/metabolismo , Ciclídeos/genética , Ciclídeos/metabolismo , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Coração/embriologia , Intestinos/embriologia , Intestinos/metabolismo , Mesoderma/embriologia , Mesoderma/metabolismo , Miocárdio/metabolismo , Sistema Nervoso Periférico/embriologia , Sistema Nervoso Periférico/metabolismo , Homologia de Sequência , Crânio/embriologia , Crânio/metabolismo , Dente/embriologia , Dente/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
12.
Sci Rep ; 11(1): 12118, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108558

RESUMO

Human identification from burned remains poses a challenge to forensic laboratories, and DNA profiling is widely used for this purpose. Our aim was to evaluate the effect of temperature on DNA degradation in human teeth. Thirty teeth were exposed to temperatures of 100, 200, or 400 °C for 60 min. DNA was quantified by Real-Time qPCR (Quantifiler Human DNA Quantification Kit) and fluorescence spectroscopy (Qubit 3.0 Fluorometer). DNA degradation was evaluated by using STR markers (AmpFLSTR Identifiler Plus PCR Amplification Kit) to determine the allele and locus dropout, inter-locus balance, and degradation slope (observed (Oa) to expected (Ea) locus peak height ratio against the molecular weight). Most of the genomic DNA was degraded between 100 °C and 200 °C. At 100 °C, locus dropout ratios showed significant differences between the largest loci (FGA, D7S820, D18S51, D16S539, D2S1338 and CSF1PO) and amelogenin. Inter-locus balance values significantly differed between all dye channels except between NED and PET. The dropout ratio between D18S51 (NED) and amelogenin (PET) can be recommended for the evaluation of DNA degradation. The Oa/Ea regression model can predict locus peak heights in DNA degradation (R2 = 0.7881). These findings may be useful to assess the reliability of DNA typing for human identification in teeth subjected to prolonged incineration.


Assuntos
DNA/metabolismo , Resposta ao Choque Térmico , Dente/metabolismo , Adulto , Idoso , DNA/análise , DNA/genética , Impressões Digitais de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Dente/patologia , Adulto Jovem
13.
PLoS One ; 16(5): e0250429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34038418

RESUMO

Dentin Sialoprotein (DSP) and phosphophoryn (PP) are two most dominant non-collagenous proteins in dentin, which are the cleavage products of the DSPP (dentin sialophosphoprotein) precursor protein. The absence of the DSPP gene in DSPP knock-out (KO) mice results in characteristics that are consistent with dentinogenesis imperfecta type III in humans. Symptoms include thin dentin, bigger pulp chamber with frequent pulp exposure as well as abnormal epithelial-mesenchymal interactions, and the appearance of chondrocyte-like cells in dental pulp. To better understand how DSPP influences tooth development and dentin formation, we used a bacterial artificial chromosome transgene construct (BAC-DSPP) that contained the complete DSPP gene and promoter to generate BAC-DSPP transgenic mice directly in a mouse DSPP KO background. Two BAC-DSPP transgenic mouse strains were generated and characterized. DSPP mRNA expression in BAC-DSPP Strain A incisors was similar to that from wild-type (wt) mice. DSPP mRNA expression in BAC-DSPP Strain B animals was only 10% that of wt mice. PP protein content in Strain A incisors was 25% of that found in wt mice, which was sufficient to completely rescue the DSPP KO defect in mineral density, since microCT dentin mineral density analysis in 21-day postnatal animal molars showed essentially identical mineral density in both strain A and wt mice. Strain B mouse incisors, with 5% PP expression, only partially rescued the DSPP KO defect in mineral density, as microCT scans of 21-day postnatal animal molars indicated a reduced dentin mineral density compared to wt mice, though the mineral density was still increased over that of DSPP KO. Furthermore, our findings showed that DSPP dosage in Strain A was sufficient to rescue the DSPP KO defect in terms of epithelial-mesenchymal interactions, odontoblast lineage maintenance, along with normal dentin thickness and normal mineral density while DSPP gene dosage in Strain B only partially rescued the aforementioned DSPP KO defect.


Assuntos
Dentina/metabolismo , Proteínas da Matriz Extracelular/genética , Fosfoproteínas/genética , Sialoglicoproteínas/genética , Dente/crescimento & desenvolvimento , Animais , Cromossomos Artificiais Bacterianos/genética , Colágeno Tipo II , Dentina/diagnóstico por imagem , Dentina/patologia , Proteínas da Matriz Extracelular/deficiência , Proteínas da Matriz Extracelular/metabolismo , Incisivo/metabolismo , Incisivo/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Minerais/análise , Fosfoproteínas/deficiência , Fosfoproteínas/metabolismo , RNA Mensageiro/metabolismo , Sialoglicoproteínas/deficiência , Sialoglicoproteínas/metabolismo , Dente/metabolismo , Microtomografia por Raio-X
14.
Pol J Vet Sci ; 24(1): 151-157, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33847101

RESUMO

The last biomonitoring study in Poland on intoxication with fluoride compounds of deer was conducted almost two decades ago. Given the fact that fluoride level in air and water is not widely monitored in Poland, it is justified to undertake monitoring of F- levels in people and other long-lived mammals. This paper provides the assessment of the present level of fluoride accumulation in mineralized tissue of large herbivorous mammals. The aim of the present study was to determine fluoride concentration in teeth of deer inhabiting the areas of Poland which are industrially uncontaminated with fluoride compounds, to establish possible correlations between the analysed parameters, and to provide a comparison of the present results with those obtained in other studies. Mean concentration of fluoride in all analysed samples amounted to 231.0 F mg/kg, with the minimum value of 22.0 F mg/kg and the maximum of 935.0 F mg/kg. This results from the development of industry and a widespread use of fluoride-supplemented caries prevention products which contributes to an intense accumulation of these substances in vertebrates, predominantly in mineralized tissue.


Assuntos
Cervos/metabolismo , Poluentes Ambientais/química , Fluoretos/química , Resíduos Industriais , Dente/química , Animais , Cervos/classificação , Monitoramento Ambiental , Poluentes Ambientais/metabolismo , Fluoretos/metabolismo , Polônia , Dente/metabolismo
15.
Proc Natl Acad Sci U S A ; 118(17)2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33875585

RESUMO

The role of natural selection in the evolution of trait complexity can be characterized by testing hypothesized links between complex forms and their functions across species. Predatory venoms are composed of multiple proteins that collectively function to incapacitate prey. Venom complexity fluctuates over evolutionary timescales, with apparent increases and decreases in complexity, and yet the causes of this variation are unclear. We tested alternative hypotheses linking venom complexity and ecological sources of selection from diet in the largest clade of front-fanged venomous snakes in North America: the rattlesnakes, copperheads, cantils, and cottonmouths. We generated independent transcriptomic and proteomic measures of venom complexity and collated several natural history studies to quantify dietary variation. We then constructed genome-scale phylogenies for these snakes for comparative analyses. Strikingly, prey phylogenetic diversity was more strongly correlated to venom complexity than was overall prey species diversity, specifically implicating prey species' divergence, rather than the number of lineages alone, in the evolution of complexity. Prey phylogenetic diversity further predicted transcriptomic complexity of three of the four largest gene families in viper venom, showing that complexity evolution is a concerted response among many independent gene families. We suggest that the phylogenetic diversity of prey measures functionally relevant divergence in the targets of venom, a claim supported by sequence diversity in the coagulation cascade targets of venom. Our results support the general concept that the diversity of species in an ecological community is more important than their overall number in determining evolutionary patterns in predator trait complexity.


Assuntos
Crotalinae/genética , Dieta/tendências , Venenos de Serpentes/genética , Adaptação Biológica/genética , Animais , Crotalinae/metabolismo , Dieta/veterinária , Expressão Gênica/genética , América do Norte , Filogenia , Comportamento Predatório/fisiologia , Proteômica/métodos , Seleção Genética/genética , Venenos de Serpentes/metabolismo , Dente/metabolismo , Transcriptoma/genética
16.
Cells ; 10(3)2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652662

RESUMO

Tissue regeneration in dentistry has demonstrated impressive progress over during the last decades compared to other medical sciences [...].


Assuntos
Células/metabolismo , Engenharia Tecidual/métodos , Dente/metabolismo , Humanos , Dente/citologia
17.
Dev Dyn ; 250(10): 1494-1504, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33760336

RESUMO

BACKGROUND: Unlike many vertebrates with continuous dental replacement, mammals have a maximum of two dental generations. Due to the absence of dental replacement in the laboratory mouse, the mechanisms of the mammalian tooth replacement system are poorly known. In this study, we use the European rabbit as a model for mammalian tooth development and replacement. RESULTS: We provide data on some key regulators of tooth development. We detected the presence of SOX2 in both the replacement dental lamina and the rudimentary successional dental lamina of unreplaced molars, indicating that SOX2 may not be sufficient to initiate and maintain tooth replacement. We showed that Shh does not seem to be directly involved in tooth replacement. The transient presence of the rudimentary successional dental lamina in the molar allowed us to identify genes that could be essential for the initiation or the maintenance of tooth replacement. Hence, the locations of Sostdc1, RUNX2, and LEF1 vary between the deciduous premolar, the replacement premolar, and the molar, indicating possible roles in tooth replacement. CONCLUSION: According to our observations, initiation and the maintenance of tooth replacement correlate with the presence of LEF1+ cells and the absence of both mesenchymal RUNX2 and epithelial Sostdc1+ cells.


Assuntos
Expressão Gênica , Odontogênese/efeitos dos fármacos , Fatores de Transcrição SOXB1/metabolismo , Dente/crescimento & desenvolvimento , Animais , Subunidades alfa de Fatores de Ligação ao Core/genética , Subunidades alfa de Fatores de Ligação ao Core/metabolismo , Coelhos , Fatores de Transcrição SOXB1/genética , Dente/metabolismo
18.
Chem Res Toxicol ; 34(3): 880-891, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33507734

RESUMO

Uranium-238 (238U), a long-lived radiometal, is widespread in the environment because of both naturally occurring processes and anthropogenic processes. The ingestion or inhalation of large amounts of U is a major threat to humans, and its toxicity is considered mostly chemical rather than radiological. Therefore, a way to remove uranium ingested by humans from uranium-contaminated water or from the air is critically needed. This study investigated the uranium uptake by hydroxyapatite (HAP), a compound found in human bone and teeth. The uptake of U by teeth is a result of U transport as dissolved uranyl (UO22+) in contaminated water, and U adsorption has been linked to delays in both tooth eruption and development. In this present work, the influence of pH, contact time, initial U concentration, and buffer solution on the uptake and removal of U in synthetic HAP was investigated and modeled. The influence of pH (pH of human saliva, 6.7-7.4) on the uptake of uranyl was negligible. Furthermore, the kinetics were extremely fast; in one second of exposure, 98% of uranyl was uptaken by HAP. The uptake followed pseudo-second-order kinetics and a Freundlich isotherm model. A 0.2 M sodium carbonate solution removed all the uranyl from HAP after 1 h. Another series of in vitro tests were performed with real teeth as targets. We found that, for a 50 mg/L U in PBS solution adjusted to physiological pH, ∼35% of the uranyl was uptaken by the tooth after 1 h, following pseudo-first-order kinetics. Among several washing solutions tested, a commercially available carbonate, as well as a commercially available fluoride solution, enabled removal of all the uranyl taken up by the teeth.


Assuntos
Dente/metabolismo , Urânio/metabolismo , Durapatita/química , Durapatita/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Dente/química , Urânio/química , Urânio/isolamento & purificação
19.
Cell Signal ; 78: 109877, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33296740

RESUMO

Tooth and bone are independent tissues with a close relationship. Both are composed of a highly calcified outer structure and soft inner tissue, and both are constantly under mechanical stress. In particular, the alveolar bone and tooth constitute an occlusion system and suffer from masticatory and occlusal force. Thus, mechanotransduction is a key process in many developmental, physiological and pathological processes in tooth and bone. Mechanosensitive ion channels such as Piezo1 and Piezo2 are important participants in mechanotransduction, but their functions in tooth and bone are poorly understood. This review summarizes our current understanding of mechanosensitive ion channels and their roles in tooth and bone tissues. Research in these areas may shed new light on the regulation of tooth and bone tissues and potential treatments for diseases affecting these tissues.


Assuntos
Osso e Ossos/metabolismo , Canais Iônicos/metabolismo , Mecanotransdução Celular , Dente/metabolismo , Animais , Humanos
20.
Int J Mol Sci ; 21(21)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138041

RESUMO

FUSE binding protein 1 (Fubp1), a regulator of the c-Myc transcription factor and a DNA/RNA-binding protein, plays important roles in the regulation of gene transcription and cellular physiology. In this study, to reveal the precise developmental function of Fubp1, we examined the detailed expression pattern and developmental function of Fubp1 during tooth morphogenesis by RT-qPCR, in situ hybridization, and knock-down study using in vitro organ cultivation methods. In embryogenesis, Fubp1 is obviously expressed in the enamel organ and condensed mesenchyme, known to be important for proper tooth formation. Knocking down Fubp1 at E14 for two days, showed the altered expression patterns of tooth development related signalling molecules, including Bmps and Fgf4. In addition, transient knock-down of Fubp1 at E14 revealed changes in the localization patterns of c-Myc and cell proliferation in epithelium and mesenchyme, related with altered tooth morphogenesis. These results also showed the decreased amelogenin and dentin sialophosphoprotein expressions and disrupted enamel rod and interrod formation in one- and three-week renal transplanted teeth respectively. Thus, our results suggested that Fubp1 plays a modulating role during dentinogenesis and amelogenesis by regulating the expression pattern of signalling molecules to achieve the proper structural formation of hard tissue matrices and crown morphogenesis in mice molar development.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Embrião de Mamíferos/citologia , Regulação da Expressão Gênica no Desenvolvimento , Morfogênese , Odontogênese , Proteínas de Ligação a RNA/metabolismo , Dente/embriologia , Animais , Proliferação de Células , Proteínas de Ligação a DNA/genética , Embrião de Mamíferos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Dente/metabolismo
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