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1.
Int J Mol Sci ; 20(17)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31480549

RESUMO

Normal mammalian palatogenesis is a complex process that requires the occurrence of a tightly regulated series of specific and sequentially regulated cellular events. Cleft lip/palate (CLP), the most frequent craniofacial malformation birth defects, may occur if any of these events undergo abnormal interference. Such defects not only affect the patients, but also pose a financial risk for the families. In our recent study, the miniature pig was shown to be a valuable alternative large animal model for exploring human palate development by histology. However, few reports exist in the literature to document gene expression and function during swine palatogenesis. To better understand the genetic regulation of palate development, an mRNA expression profiling analysis was performed on miniature pigs, Sus scrofa. Five key developmental stages of miniature pigs from embryonic days (E) 30-50 were selected for transcriptome sequencing. Gene expression profiles in different palate development stages of miniature pigs were identified. Nine hundred twenty significant differentially expressed genes were identified, and the functional characteristics of these genes were determined by gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Some of these genes were associated with HH (hedgehog), WNT (wingless-type mouse mammary tumor virus integration site family), and MAPK (mitogen-activated protein kinase) signaling, etc., which were shown in the literature to affect palate development, while some genes, such as HIP (hedgehog interacting protein), WNT16, MAPK10, and LAMC2 (laminin subunit gamma 2), were additions to the current understanding of palate development. The present study provided a comprehensive analysis for understanding the dynamic gene regulation during palate development and provided potential ideas and resources to further study normal palate development and the etiology of cleft palate.


Assuntos
Morfogênese , Palato/crescimento & desenvolvimento , Transdução de Sinais , Porco Miniatura/crescimento & desenvolvimento , Transcriptoma , Animais , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Hedgehog/metabolismo , Sistema de Sinalização das MAP Quinases , Análise de Sequência de RNA , Suínos , Porco Miniatura/genética , Via de Sinalização Wnt
2.
Gene Expr Patterns ; 34: 119062, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31226309

RESUMO

Periodic patterning of iterative structures is a fundamental process during embryonic development, since these structures are diverse across the animal kingdom. Therefore, elucidating the molecular mechanisms in the formation of these structures promotes understanding of the process of organogenesis. Periodically patterned ridges, palatal rugae (situated on the hard palate of mammals), are an excellent experimental model to clarify the molecular mechanisms involved in the formation of periodic patterning of iterative structures. Primary cilia are involved in many biological events, including the regulation of signaling pathways such as Shh and non-canonical Wnt signaling. However, the role of primary cilia in the development of palatal rugae remains unclear. We found that primary cilia were localized to the oral cavity side of the interplacode epithelium of the palatal rugae, whereas restricted localization of primary cilia could not be detected in other regions. Next, we generated mice with a placodal conditional deletion of the primary cilia protein Ift88, using ShhCre mice (Ift88 fl/fl;ShhCre). Highly disorganized palatal rugae were observed in Ift88 fl/fl;ShhCre mice. Furthermore, by comparative in situ hybridization analysis, many Shh and non-canonical Wnt signaling-related molecules showed spatiotemporal expression patterns during palatal rugae development, including restricted expression in the epithelium (placodes and interplacodes) and mesenchyme. Some of these expression were found to be altered in Ift88 fl/fl;ShhCre mice. Primary cilia is thus involved in development of palatal rugae.


Assuntos
Padronização Corporal/genética , Cílios/genética , Palato/crescimento & desenvolvimento , Animais , Cílios/fisiologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário , Epitélio/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Masculino , Mesoderma/metabolismo , Camundongos/embriologia , Camundongos Endogâmicos , Boca , Gravidez , Transdução de Sinais/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Via de Sinalização Wnt/genética , Via de Sinalização Wnt/fisiologia
3.
Elife ; 82019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31162046

RESUMO

Epithelial fusion underlies many vital organogenic processes during embryogenesis. Disruptions to these cause a significant number of human birth defects, including ocular coloboma. We provide robust spatial-temporal staging and unique anatomical detail of optic fissure closure (OFC) in the embryonic chick, including evidence for roles of apoptosis and epithelial remodelling. We performed complementary transcriptomic profiling and show that Netrin-1 (NTN1) is precisely expressed in the chick fissure margin during fusion but is immediately downregulated after fusion. We further provide a combination of protein localisation and phenotypic evidence in chick, humans, mice and zebrafish that Netrin-1 has an evolutionarily conserved and essential requirement for OFC, and is likely to have an important role in palate fusion. Our data suggest that NTN1 is a strong candidate locus for human coloboma and other multi-system developmental fusion defects, and show that chick OFC is a powerful model for epithelial fusion research.


Assuntos
Coloboma/genética , Evolução Molecular , Olho/crescimento & desenvolvimento , Netrina-1/genética , Animais , Apoptose/genética , Embrião de Galinha , Galinhas , Coloboma/patologia , Sequência Conservada/genética , Células Epiteliais/metabolismo , Olho/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Camundongos , Palato/crescimento & desenvolvimento , Palato/patologia , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento
4.
Clin Oral Investig ; 23(10): 3705-3712, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30635787

RESUMO

OBJECTIVES: The aim of this study was to develop an accurate and intuitive semi-automatic segmentation technique to calculate an average maxillary arch and palatal growth profile for healthy newborns in their first year of life. MATERIALS AND METHODS: Seventy babies born between 1985 and 1988 were included in this study. Each child had five impressions made in the first year after birth that were digitalized. A semi-automatic segmentation tool was developed and used to assess the maxillary dimensions. Finally, random effect models were built to describe the growth and build a simulation population of 10,000 newborns. The segmentation was tested for inter- and intra-observer variability. RESULTS: The Pearson correlation coefficient for each of the variables was between 0.94 and 1.00, indicating high inter-observer agreement. The paired sample t test showed that, except for the tuberosity distance, there were small, but significant differences in the landmark placements between observers. Intra-observer repeatability was high, with Pearson correlation coefficients ranging from 0.87 to 1.00 for all measurements, and the mean differences were not significant. A third or second degree growth curve could be successfully made for each parameter. CONCLUSIONS: These findings indicated this method could be used for objective clinical evaluation of maxillary growth. CLINICAL RELEVANCE: The resulting growth models can be used for growth studies in healthy newborns and for growth and treatment outcome studies in children with cleft lip and palate or other craniofacial anomalies.


Assuntos
Maxila/crescimento & desenvolvimento , Fenda Labial , Fissura Palatina , Arco Dental/crescimento & desenvolvimento , Humanos , Lactente , Recém-Nascido , Variações Dependentes do Observador , Palato/crescimento & desenvolvimento
5.
Angle Orthod ; 89(1): 71-77, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30230376

RESUMO

OBJECTIVES: To assess reliability and reproducibility of the individual assessment of midpalatal suture maturation in computed tomography among orthodontists and radiologists for potential diagnosis application. MATERIALS AND METHODS: Sixty axial slices from cone-beam computed tomography and multi-slice CT scans of patients aged between 11 and 21 years old (33 females and 27 males) were selected. For the investigation of reliability and reproducibility of the method, two groups of examiners were established. The first group consisted of 11 orthodontists and the second consisted of 10 radiologists. Each group examined the images and performed individual assessment of the midpalatal suture maturation method twice within an interval of 21 days. During the first and second analyses, the sequence of images was randomized to reduce potential bias. Weighted Cohen's kappa was performed to assess inter- and intra-examiners' agreement. The percentage of perfect agreement and the number of stages apart for each disagreement were calculated. The significance level was P < .05. RESULTS: The overall inter-examiner agreement was satisfactory in the first (kappaw: 0.37) and the second (kappaw: 0.34) analyses. Intra-examiner agreement outcomes were similar between orthodontists (kappaw: 0.44) and radiologists (kappaw: 0.41). The percentage of perfect agreement was 43.2%. CONCLUSIONS: The method for individual assessment of midpalatal suture maturation revealed potential reliability and reproducibility. However, the agreement rate observed in the present study was not high enough for a method designed for routine clinical applications.


Assuntos
Suturas Cranianas , Palato , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Criança , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Masculino , Palato/crescimento & desenvolvimento , Reprodutibilidade dos Testes , Adulto Jovem
6.
Anat Rec (Hoboken) ; 301(11): 1820-1833, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30290073

RESUMO

Although minor salivary glands play a significant functional role in the oral cavity, their developmental morphology and cell differentiation has been scarcely studied. This study aimed to describe the development of rat palatine glands with regard to the ultrastructural morphology of the secretory cells and surrounding myoepithelial cells (MECs). Palatine glands from rats at embryonic ages (E) 18 and 20 days, and postnatal days (PN) 0, 3, 7, 10, 13, 21, 30, 42, and 60 were fixed and prepared for morphological analysis and immunocytochemical labeling of alpha-smooth muscle actin (α-SMA). At E18, epithelial cords were observed extending from the palatal epithelium and showed negative reactivity to α-SMA. After luminization at E20, the cells of immature acini accumulated secretory granules of various densities: electron-dense, electron-lucent and some empty-appearing granules. MECs were poorly differentiated at E20 and exhibited only slight α-SMA expression. At birth, mucous and serous cells were typically located around a common lumen. Thereafter, serous cells began to move to the periphery to form demilunes by PN7. The mucous secretory granules of intermediate electron density became predominant around PN13. At PN21, these granules were dramatically reduced in number and most of the acini in adults contained acinar cells with numerous electron-lucent granules, and a few serous demilune cells with electron-dense granules. After birth, MECs progressively accumulated actin microfilaments until prominent α-SMA expressing MECs invested the acini and the proximal part of the intercalated ducts in the adult. Anat Rec, 301:1820-1833, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Desenvolvimento Embrionário/fisiologia , Microscopia Eletrônica/métodos , Glândulas Salivares/embriologia , Glândulas Salivares/ultraestrutura , Animais , Animais Recém-Nascidos , Feminino , Masculino , Palato/embriologia , Palato/crescimento & desenvolvimento , Palato/ultraestrutura , Ratos , Ratos Sprague-Dawley , Glândulas Salivares/crescimento & desenvolvimento
7.
Biochem Biophys Res Commun ; 506(1): 223-230, 2018 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-30343888

RESUMO

Mammalian palate separates the oral and nasal cavities for normal feeding, breathing and speech. The palatal shelves are a pair of maxillary prominences that consist of the neural crest-derived mesenchyme and surrounding epithelium. Palatogenesis is completed by the fusion of the midline epithelial seam (MES) after the medial edge epithelium (MEE) cells make contact between the palatal shelves. Various cellular and molecular events, such as apoptosis, cell proliferation, cell migration, and epithelial-mesenchymal transition (EMT), are involved in palatogenesis. The Zeb family of transcription factors is an essential player during normal embryonic development. The distinct role of the Zeb family has not been thoroughly elucidated to date. In mouse palate, the Zeb family factors are expressed in the palatal mesenchyme until MEE contact. Interestingly, the expression of the Zeb family has also been observed in MES, which is already fused with the mesenchymal region. The regulatory roles of the Zeb family in palatogenesis have not been elucidated to date. The purpose of this study is to determine the Zeb family effects on the cellular events. To investigate the functions of the Zeb family, siRNA targeting Zeb family was used to treat in vitro organ culture for temporary inhibition of the Zeb family during palatogenesis. In the cultured palate containing siRNA, MES was clearly observed, and E-cadherin, an epithelial marker, was still expressed. Inhibition of the Zeb family results in the suppression of apoptosis, increased cell proliferation, and defective cell migration in the developing palate. Our data suggest that the Zeb family plays multiple roles in the stimulation and inhibition of apoptosis and cell proliferation and efficient mesenchymal cell migration during palatogenesis.


Assuntos
Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Palato/embriologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/fisiologia , Animais , Movimento Celular , Proliferação de Células , Células Epiteliais , Proteínas de Homeodomínio/fisiologia , Camundongos , Técnicas de Cultura de Órgãos , Palato/crescimento & desenvolvimento , RNA Interferente Pequeno/farmacologia , Fatores de Transcrição , Homeobox 1 de Ligação a E-box em Dedo de Zinco/antagonistas & inibidores
8.
Bull Tokyo Dent Coll ; 59(3): 183-191, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30224612

RESUMO

The purpose of this study was to investigate the long-term effects of two-stage palatoplasty on the morphology of the maxillary alveolar arch and occlusion using plaster models of the maxilla and mandible obtained from patients with unilateral complete cleft lip and palate who also underwent orthodontic treatment. A total of 20 patients undergoing two-stage palatoplasty by Perko's method (Group T) were enrolled. Plaster models of the maxilla and mandible were obtained from each patient at Time 1, on commencement of orthodontic treatment in the mixed dentition period; at Time 2, on that of orthodontic treatment in the permanent dentition period; and at Time 3, on completion of active orthodontic treatment. Analysis of occlusion and morphological analysis were performed using a 3-dimensional measuring system. The results were compared with 15 patients who underwent one-stage palatoplasty by the push-back method using a mucoperiosteal flap (Group P). Alveolar morphology and the relationship between the maxilla and mandible were satisfactory in Group T. The palates in Group T were deeper and larger than those in Group P. Alveolar collapse in Group T was milder, and impairment of the alveolar morphology less notable than in Group P, as surgical invasion to the anterior alveolar region was avoided during the palatal growth period. These results suggest that two-stage palatoplasty is advantageous for jaw development.


Assuntos
Fissura Palatina/terapia , Palato/crescimento & desenvolvimento , Criança , Fenda Labial/terapia , Modelos Dentários , Feminino , Humanos , Imageamento Tridimensional , Masculino , Ortodontia Corretiva
9.
Sci Rep ; 8(1): 11208, 2018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-30046048

RESUMO

Runx1 deficiency results in an anteriorly specific cleft palate at the boundary between the primary and secondary palates and in the first rugae area of the secondary palate in mice. However, the cellular and molecular pathogenesis underlying such regional specificity remain unknown. In this study, Runx1 epithelial-specific deletion led to the failed disintegration of the contacting palatal epithelium and markedly downregulated Tgfb3 expression in the primary palate and nasal septum. In culture, TGFB3 protein rescued the clefting of the mutant. Furthermore, Stat3 phosphorylation was disturbed in the corresponding cleft regions in Runx1 mutants. The Stat3 function was manifested by palatal fusion defects in culture following Stat3 inhibitor treatment with significant downregulation of Tgfb3. Tgfb3 is therefore a critical target of Runx1 signaling, and this signaling axis could be mediated by Stat3 activation. Interestingly, the expression of Socs3, an inhibitor of Stat3, was specific in the primary palate and upregulated by Runx1 deficiency. Thus, the involvement of Socs3 in Runx1-Tgfb3 signaling might explain, at least in part, the anteriorly specific downregulation of Tgfb3 expression and Stat3 activity in Runx1 mutants. This is the first study to show that the novel Runx1-Stat3-Tgfb3 axis is essential in anterior palatogenesis.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Desenvolvimento Embrionário/genética , Palato/crescimento & desenvolvimento , Fator de Transcrição STAT3/genética , Fator de Crescimento Transformador beta3/genética , Animais , Apoptose/genética , Fissura Palatina/genética , Fissura Palatina/patologia , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento/genética , Camundongos , Palato/metabolismo , Transdução de Sinais/genética , Proteína 3 Supressora da Sinalização de Citocinas/genética
10.
BMC Genomics ; 19(1): 429, 2018 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-29866044

RESUMO

BACKGROUND: Microdeletion of chromosome 22q11 is associated with significant developmental anomalies, including disruption of the cardiac outflow tract, thymic/parathyroid aplasia and cleft palate. Amongst the genes within this region, TBX1 is a major candidate for many of these developmental defects. Targeted deletion of Tbx1 in the mouse has provided significant insight into the function of this transcription factor during early development of the cardiac and pharyngeal systems. However, less is known about its role during palatogenesis. To assess the influence of Tbx1 function on gene expression profile within the developing palate we performed a microarray screen using total RNA isolated from the secondary palate of E13.5 mouse embryos wild type, heterozygous and mutant for Tbx1. RESULTS: Expression-level filtering and statistical analysis revealed a total of 577 genes differentially expressed across genotypes. Data were clustered into 3 groups based on comparison between genotypes. Group A was composed of differentially expressed genes in mutant compared to wild type (n = 89); Group B included differentially expressed genes in heterozygous compared to wild type (n = 400) and Group C included differentially expressed genes in mutant compared to heterozygous (n = 88). High-throughput quantitative real-time PCR (RT-PCR) confirmed a total of 27 genes significantly changed between wild type and mutant; and 27 genes between heterozygote and mutant. Amongst these, the majority were present in both groups A and C (26 genes). Associations existed with hypertrophic cardiomyopathy, cardiac muscle contraction, dilated cardiomyopathy, focal adhesion, tight junction and calcium signalling pathways. No significant differences in gene expression were found between wild type and heterozygous palatal shelves. CONCLUSIONS: Significant differences in gene expression profile within the secondary palate of wild type and mutant embryos is consistent with a primary role for Tbx1 during palatogenesis.


Assuntos
Deleção de Genes , Perfilação da Expressão Gênica , Palato/crescimento & desenvolvimento , Proteínas com Domínio T/deficiência , Proteínas com Domínio T/genética , Animais , Feminino , Genótipo , Camundongos
11.
Reprod Toxicol ; 77: 137-142, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29526646

RESUMO

Numerous studies have been conducted to understand the molecular mechanisms controlling mammalian secondary palate development such as growth, reorientation and fusion. However, little is known about the signaling factors regulating palate initiation. Mouse fibroblast growth factor (FGF) receptor 2 gene (Fgfr2) is expressed on E11.5 in the palate outgrowth within the maxillary process, in a region that is responsible for palate cell specification and shelf initiation. Fgfr2 continues to express in palate on E12.5 and E13.5 in both epithelial and mesenchymal cells, and inactivation of Fgfr2 expression in mesenchymal cells using floxed Fgfr2 allele and Osr2-Cre leads to cleft palate at various stages including reorientation, horizontal growth and fusion. Notably, some mutant embryos displayed no sign of palate shelf formation suggesting that FGF receptor 2 mediated FGF signaling may play an important role in palate initiation.


Assuntos
Palato/crescimento & desenvolvimento , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Animais , Fissura Palatina/genética , Feminino , Mutação com Perda de Função , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Palato/citologia , Palato/metabolismo
12.
Dental Press J Orthod ; 23(6): 16-29, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30672982

RESUMO

OBJECTIVE: To evaluate topographic and temporal aspects of premaxillary bone and premaxillary-maxillary suture, since they are fundamental anatomical elements little explored clinically. METHODS: 1,138 human dry skulls were evaluated, of which 116 (10.19%) of the specimens were children, and 1,022 (89.81%) were adults. The skulls were photographed and the percentage of premaxillary-maxillary suture opening was determined. Subsequently the data were tabulated and submitted to statistical analysis, adopting a level of significance of 5%. RESULTS: The progression of premaxillary suture closure from birth to 12 years of age was 3.72% per year. In 100% of the skulls up to 12 years, the premaxillary-maxillary suture open in the palatal region was observed, while 6.16% of adults presented different degrees of opening. CONCLUSIONS: The premaxilla exists in an independent way within the maxillary complex and the presence of the premaxilla-maxillary suture justifies the success of anteroposterior expansions to stimulate the growth of the middle third of the face, solving anatomical and functional problems.


Assuntos
Suturas Cranianas/anatomia & histologia , Suturas Cranianas/crescimento & desenvolvimento , Maxila/anatomia & histologia , Maxila/crescimento & desenvolvimento , Desenvolvimento Maxilofacial/fisiologia , Crânio/anatomia & histologia , Crânio/crescimento & desenvolvimento , Adulto , Fatores Etários , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Maxila/diagnóstico por imagem , Ortodontia Corretiva , Palato/anatomia & histologia , Palato/diagnóstico por imagem , Palato/crescimento & desenvolvimento , Crânio/diagnóstico por imagem
13.
Sci Rep ; 7(1): 5148, 2017 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-28698574

RESUMO

Normal cell cycle progression and proliferation of palatal mesenchymal cells are important for palatal development. As targets of miR-17-92, E2F transcription factors family has been suggested to induce the transcription of miR-17-92 in several cell types. In the present study, we sought to investigate whether this negative feedback loop exists in mouse PMCs and what the function of this negative feedback loop would be in palatal mesenchymal cells. Using GeneMANIA, we revealed that the most important function of experimentally verified targets of miR-17-92 is cell cycle regulation. E2F1 and E2F3, but not E2F2, were extensively expressed in mouse palate. Over-expression of E2F1 significantly increased the expression of all the members of miR-17-92. After increased by E2F1, miR-17 and miR-20a may negatively target E2F1, and thereby prevent the cells from excessive proliferation. We suggest that the negative feedback loop between E2F1 and miR-17-92 may contribute to palatal development by regulating the proliferation and cell cycle of palatal mesenchymal cells.


Assuntos
Fator de Transcrição E2F1/genética , Fator de Transcrição E2F1/metabolismo , MicroRNAs/genética , Palato/crescimento & desenvolvimento , Animais , Ciclo Celular , Linhagem Celular , Proliferação de Células , Fator de Transcrição E2F2/genética , Fator de Transcrição E2F2/metabolismo , Fator de Transcrição E2F3/genética , Fator de Transcrição E2F3/metabolismo , Retroalimentação Fisiológica , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Família Multigênica , Palato/citologia , Palato/metabolismo
14.
Am J Orthod Dentofacial Orthop ; 152(1): 42-48, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28651767

RESUMO

INTRODUCTION: We used cone-beam computed tomography to evaluate the maturation stages of the midpalatal sutures in children aged 11 to 15 years old. Maxillary expansion is successful for most patients in this age group, so we sought to identify the status of suture maturation in these subjects to use as a comparison for the prognosis of rapid maxillary expansion in older patients. METHODS: Tomographic images in axial sections of the midpalatal sutures from 84 children (40 boys, 44 girls; ages, 11-15 years) were classified using a scale denoting the maturation stage of the midpalatal suture (A, B, C, D, and E). The chi-square test was applied to evaluate suture stages by sex and age groups. RESULTS: Stage A was observed in only one 11-year-old girl. Stage B was present at all ages but was more prevalent in those less than 13 years of age. Stage C was the most prevalent in all evaluated ages. Stages D and E showed low prevalence rates. There were higher prevalences of the early stages of maturation in boys. CONCLUSIONS: The results of this study, which showed dominant prevalence of stage C, suggest that conventional, nonsurgical rapid maxillary expansion performed in patients over 15 years old is justified by a satisfactory prognosis when assessment of the sutural status indicates stage C.


Assuntos
Técnica de Expansão Palatina , Palato/crescimento & desenvolvimento , Adolescente , Fatores Etários , Criança , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Masculino , Técnica de Expansão Palatina/instrumentação , Palato/diagnóstico por imagem , Fatores Sexuais , Resultado do Tratamento
15.
Am J Orthod Dentofacial Orthop ; 151(5): 921-928, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28457270

RESUMO

INTRODUCTION: Buccolingual inclinations of the maxillary permanent molars and intermolar widths increase with growth for Class I subjects. Changes for untreated Class II subjects have not yet been assessed. The aim of this study was to test the hypothesis that changes in palatal inclination of the maxillary molars and intermolar width throughout growth vary between Class I and Class II molar occlusions. METHODS: Patients were selected from the Forsyth/Moorrees Twin Study. Dental models taken for 6 consecutive years of 55 untreated subjects (28 with Angle Class I and 27 with Angle Class II occlusion) were scanned. The images were superimposed on the palatal rugae, and the angle between a reference plane and the buccolingual inclination plane was used to calculate the buccolingual molar inclination at each time point. The distance between lingual groove points was used to calculate the intermolar width. RESULTS: All molars showed increasing palatal inclinations over the 6 years. The change for each time interval was statistically significant. Class I subjects demonstrated significantly greater palatal inclination at each time point. The molar inclination changed by means of 4.99° for Class I subjects and 6.25° for Class II subjects. Intermolar width increased continuously (P <0.001) and was significantly greater (P <0.05) for Class I patients. CONCLUSIONS: These results suggest that palatal inclination of the maxillary permanent first molars occurs continuously between ages 9 and 14 years, with Class II subjects showing greater changes. The intermolar width increases steadily during this time, with Class II subjects having a narrower intermolar width and less change over time.


Assuntos
Má Oclusão de Angle Classe II/patologia , Má Oclusão de Angle Classe I/patologia , Dente Molar/crescimento & desenvolvimento , Adolescente , Criança , Pré-Escolar , Arco Dental/patologia , Modelos Dentários , Feminino , Humanos , Masculino , Maxila/crescimento & desenvolvimento , Maxila/patologia , Dente Molar/patologia , Palato/crescimento & desenvolvimento , Palato/patologia , Estudos Retrospectivos
16.
Clin Anat ; 30(7): 846-854, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28459132

RESUMO

This study describes the dentoalveolar and palatal growth during the first months of life. Knowledge concerning this development is essential to avoid unwanted events such as mucosal ulcerations or restriction of growth when cleft-lip and palate (CLP) patients are treated. The results involve the generation of CAD/CAM CLP-feeding plates. Intraoral impressions from 32 healthy newborns were taken monthly for 5 months, supplemented by measurements of body weight, length, and occipital-frontal head circumference. The casts were digitalized, and two observers manually selected defined anatomical landmarks on virtual 3-D models. The distances between these landmarks were evaluted. Statistical analysis included an inter-rater agreement analysis and the determination of growth. In total, 213 casts were analyzed, with 65 models excluded because of inaccuracies in impression-taking or cast production. Overall longitudinal growth was 20.3%, whereas transversal growth reached a maximum of 21.1%. Vertical growth was 32.4% at the tuberal level. On the basis of these results, a semiautomated series of feeding plates allowing for monthly expansion could be generated. The acquired data serve as a useful reference for other pediatric and orthofacial investigations and treatments. One such application is the automated, fully virtual manufacture of CLP-feeding plates based on only one impression-taking. Our data reveal when caution is needed to prevent ulceration. The series of plates generated can minimize the time-consuming impression-taking and the production of further plaster models. The method of measurement is suitable for documentary purposes. Clin. Anat. 30:846-854, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Fenda Labial/terapia , Fissura Palatina/terapia , Métodos de Alimentação/instrumentação , Palato/crescimento & desenvolvimento , Desenho de Prótese , Alvéolo Dental/crescimento & desenvolvimento , Pontos de Referência Anatômicos , Fenda Labial/patologia , Fissura Palatina/patologia , Desenho Assistido por Computador , Humanos , Lactente , Modelos Anatômicos , Estudos Prospectivos
17.
Am J Orthod Dentofacial Orthop ; 151(3): 513-520, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28257736

RESUMO

INTRODUCTION: Head and neck skeletal anomalies or normal variants might predict the occurrence of palatally displaced impacted maxillary canines. Despite their clinical importance, studies in this regard are rare, especially when it comes to vertebral anomalies. METHODS: This case-control study was performed on cephalographs of 35 orthodontic patients (11 male, 24 female) with palatally displaced canines (PDC) and 75 patients without them (29 male, 46 female). PDC were diagnosed on panoramic and lateral cephalographs and from clinical reports. The occurrence and severity of sella turcica bridge and the atlas ponticulus posticus, and deficiency of the posterior atlas arch were evaluated twice on lateral cephalographs. The associations between the occurrence and level of these skeletal anomalies and variations of PDC occurrence as well as additional correlations were assessed using multivariable and bivariate statistics (α = 0.05; ß ≤0.2). RESULTS: The patients' mean age was 18.4 ± 1.9 years. In the control and patient groups, 23 (30.7%) and 21 subjects (60%) had sella turcica bridging, respectively (chi-square, P = 0.003). Ponticulus posticus was observed in 14 (18.7%) controls and 15 (42.9%) patients (chi-square, P = 0.007). Posterior atlas arch deficiency was observed in 4 (5.3%) controls and 5 (14.3%) patients (chi-square, P = 0.111). The presence of ponticulus posticus and sella turcica bridging might be associated with increased odds of PDC occurrence for about odds ratios of 3.1 and 3.5 times, respectively (binary logistic regression). CONCLUSIONS: PDC is positively associated with the occurrence and severity of sella turcica bridging and ponticulus posticus. The association between PDC and posterior atlas arch deficiency was inconclusive.


Assuntos
Atlas Cervical/anormalidades , Dente Canino/patologia , Palato/anormalidades , Sela Túrcica/anormalidades , Dente Impactado/diagnóstico por imagem , Adolescente , Estudos de Casos e Controles , Cefalometria , Atlas Cervical/crescimento & desenvolvimento , Feminino , Humanos , Masculino , Maxila/diagnóstico por imagem , Palato/crescimento & desenvolvimento , Radiografia Panorâmica , Sela Túrcica/diagnóstico por imagem
18.
Am J Orthod Dentofacial Orthop ; 151(2): 267-276, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28153155

RESUMO

INTRODUCTION: During adolescence, increasing interdigitation of the midpalatal suture increases resistance to rapid maxillary expansion (RME); this decreases its skeletal effect. In this study, we aimed at determining whether a novel measure of midpalatal suture maturity, the midpalatal suture density ratio, can be used as a valid predictor of the skeletal response to RME. METHODS: The midpalatal suture density ratio, chronologic age, cervical vertebral maturation, and the stage of midpalatal suture maturation were assessed before treatment for 30 patients (ages, 12.9 ± 2.1 years) who underwent RME as part of comprehensive orthodontic treatment. Measurements on cone-beam computed tomography scans were used to determine the proportions of prescribed expansion achieved at the greater palatine foramina, the nasal cavity, and the infraorbital foramina. RESULTS: There was a statistically significant negative correlation between the midpalatal suture density ratio and both the greater palatine foramina and the infraorbital foramina (r = -0.7877 and -0.3647, respectively; P <0.05). In contrast, chronologic age, cervical vertebral maturation, and stage of midpalatal suture maturation were not significantly correlated to any of the assessed measures of skeletal expansion (r range, -0.2209 to 0.0831; P >0.05). CONCLUSIONS: The midpalatal suture density ratio has the potential to become a useful clinical predictor of the skeletal response to RME. Conversely, chronologic age, cervical vertebral maturation, and stage of midpalatal suture maturation cannot be considered useful parameters to predict the skeletal effects of RME.


Assuntos
Determinação da Idade pelo Esqueleto , Vértebras Cervicais/crescimento & desenvolvimento , Suturas Cranianas/crescimento & desenvolvimento , Técnica de Expansão Palatina , Palato/crescimento & desenvolvimento , Adolescente , Criança , Estudos de Coortes , Tomografia Computadorizada de Feixe Cônico , Suturas Cranianas/diagnóstico por imagem , Feminino , Previsões , Humanos , Imageamento Tridimensional , Masculino , Palato/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Tempo
19.
Hum Mol Genet ; 26(5): 860-872, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28069795

RESUMO

Ciliopathies are pleiotropic human diseases resulting from defects of the primary cilium, and these patients often have cleft lip and palate. IFT88 is required for the assembly and function of the primary cilia, which mediate the activity of key developmental signaling pathways. Through whole exome sequencing of a family of three affected siblings with isolated cleft lip and palate, we discovered that they share a novel missense mutation in IFT88 (c.915G > C, p.E305D), suggesting this gene should be considered a candidate for isolated orofacial clefting. In order to evaluate the function of IFT88 in regulating craniofacial development, we generated Wnt1-Cre;Ift88fl/fl mice to eliminate Ift88 specifically in cranial neural crest (CNC) cells. Wnt1-Cre;Ift88fl/flpups died at birth due to severe craniofacial defects including bilateral cleft lip and palate and tongue agenesis, following the loss of the primary cilia in the CNC-derived palatal mesenchyme. Loss of Ift88 also resulted in a decrease in neural crest cell proliferation during early stages of palatogenesis as well as a downregulation of the Shh signaling pathway in the palatal mesenchyme. Importantly, Osr2KI-Cre;Ift88fl/flmice, in which Ift88 is lost specifically in the palatal mesenchyme, exhibit isolated cleft palate. Taken together, our results demonstrate that IFT88 has a highly conserved function within the primary cilia of the CNC-derived mesenchyme in the lip and palate region in mice and is a strong candidate as an orofacial clefting gene in humans.


Assuntos
Fenda Labial/genética , Desenvolvimento Embrionário/genética , Proteínas Supressoras de Tumor/genética , Proteína Wnt1/genética , Animais , Proliferação de Células/genética , Fenda Labial/patologia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Mesoderma/crescimento & desenvolvimento , Mesoderma/patologia , Camundongos , Crista Neural/crescimento & desenvolvimento , Crista Neural/metabolismo , Crista Neural/patologia , Palato/crescimento & desenvolvimento , Palato/patologia , Transdução de Sinais , Proteínas Supressoras de Tumor/biossíntese , Proteína Wnt1/biossíntese
20.
Sci Rep ; 6: 38398, 2016 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-27917906

RESUMO

Several mutations, located mainly in the MSX1 homeodomain, have been identified in non-syndromic tooth agenesis predominantly affecting premolars and third molars. We identified a novel frameshift mutation of the highly conserved C-terminal domain of MSX1, known as Msx homology domain 6 (MH6), in a Japanese family with non-syndromic tooth agenesis. To investigate the importance of MH6 in tooth development, Msx1 was targeted in mice with CRISPR/Cas system. Although heterozygous MH6 disruption did not alter craniofacial development, homozygous mice exhibited agenesis of lower incisors with or without cleft palate at E16.5. In addition, agenesis of the upper third molars and the lower second and third molars were observed in 4-week-old mutant mice. Although the upper second molars were present, they were abnormally small. These results suggest that the C-terminal domain of MSX1 is important for tooth and palate development, and demonstrate that that CRISPR/Cas system can be used as a tool to assess causality of human disorders in vivo and to study the importance of conserved domains in genes.


Assuntos
Anodontia/genética , Sistemas CRISPR-Cas , Fenda Labial/genética , Fissura Palatina/genética , Fator de Transcrição MSX1/genética , Dente Serotino/metabolismo , Mutação , Palato/metabolismo , Adolescente , Adulto , Animais , Anodontia/metabolismo , Anodontia/patologia , Sequência de Bases , Fenda Labial/metabolismo , Fenda Labial/patologia , Fissura Palatina/metabolismo , Fissura Palatina/patologia , Modelos Animais de Doenças , Embrião de Mamíferos , Feminino , Edição de Genes/métodos , Expressão Gênica , Loci Gênicos , Heterozigoto , Homozigoto , Humanos , Incisivo/anormalidades , Incisivo/crescimento & desenvolvimento , Incisivo/metabolismo , Fator de Transcrição MSX1/metabolismo , Masculino , Camundongos , Dente Serotino/anormalidades , Dente Serotino/crescimento & desenvolvimento , Palato/anormalidades , Palato/crescimento & desenvolvimento , Linhagem , Domínios Proteicos
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