Estrogen deficiency influences SEC23A gene expression in the odontogenic region of incisors ­ a murine model study / A deficiência de estrógeno influencia a expressão gênica de SEC23A na região odontogênica de incisivos ­ um estudo em modelo murino

Recent scientific evidence suggests a close relationship between estrogen deficiency and vitamin D- related genes. Estrogen and vitamin D were involved with alterations in odontogenesis and tooth eruption process. Objective: The aim of the present study was to evaluate the influence of estrogen deficiency on the expression of genes related to the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model. Material and Methods: This is an experimental clinical study that used female Wistar Hannover rats. The animals were randomly divided into two groups according to the intervention received: Hypoestrogenism Group ­ animals submitted to estrogen deficiency by ovariectomy surgery and Control Group ­ animals submitted to sham surgery. Surgical intervention was performed in the prepubertal period; the animals were followed throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the mRNA expression of the vitamin D-related genes AMDHD1, CYP24A1, NADSYN1 and SEC23A in the odontogenic region of incisors through real time PCR. Student's t test was used to compare means. Kruskal-Wallis test and Dunn's posttest were also used. The level of significance was 5%. Results: SEC23A was overexpressed in the estrogen deficiency condition in the odontogenic region (p=0.021). Conclusion: Estrogen deficiency may influence the expression of the SEC23A gene involved in the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model(AU)

Evidências científicas recentes sugerem uma estreita relação entre a deficiência de estrógeno e os genes relacionados à vitamina D. O estrógeno e a vitamina D estão envolvidos com alterações na odontogênese e no processo de erupção dentária. Objetivo: O objetivo do presente estudo foi avaliar a influência da deficiência de estrógeno na expressão de genes relacionados à ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino. Material e Métodos: Trata-se de um estudo clínico experimental que utilizou ratas Wistar Hannover fêmeas. Os animais foram divididos aleatoriamente em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo ­ animais submetidos à deficiência de estrógeno pela cirurgia de ovariectomia e Grupo Controle ­ animais submetidos à cirurgia simulada. A intervenção cirúrgica foi realizada no período pré-púbere; os animais foram acompanhados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão de mRNA dos genes AMDHD1, CYP24A1, NADSYN1 e SEC23A, relacionados à vitamina D, na região odontogênica de incisivos por meio de PCR em tempo real. O teste t de Student foi utilizado para comparar as médias. Também foram utilizados o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: SEC23A foi superexpresso na condição de deficiência de estrógeno na região odontogênica (p=0,021). Conclusão: A deficiência de estrógeno pode influenciar a expressão do gene SEC23A envolvido na ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino (AU)

mTORC1 signaling pathway regulates tooth repair / 国际口腔科学杂志·英文版

Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b+ tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.

Tooth number abnormality: from bench to bedside / 国际口腔科学杂志·英文版

Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.

Detección polimórfica del rs104893850 de MSX1 y rs28933373 de PAX9 en personas con agenesia dental no sindrómica / Polymorphic detection of rs104893850 of MSX1 and rs28933373 of PAX9 in people with non syndromic dental agnesia

Introducción: la agenesia dental no sindrómica (ADNS) genera efec- tos negativos en la salud oral y psicosocial de los seres humanos. El determinante genético desempeña un papel importante en su desarrollo. Objetivo: determinar la frecuencia de los polimorfismos rs104893850 de MSX1 y rs28933373 de PAX9 en pacientes de seis a 18 años con ADNS. Material y métodos: estudio transversal prolectivo en el cual se revisaron individuos de seis a 18 años sin defectos congénitos y originarios del estado de Durango. Después de haber obtenido su con- sentimiento para formar parte del estudio, se estableció el diagnóstico de ADNS a través de una inspección clínica odontológica y un examen radiográfico. Se tomó una muestra de sangre capilar para la genotipi- ficación de los polimorfismos a través de la técnica de qPCR-HRM. Resultados: de un total de 124 individuos, 77 (62%) mujeres y 47 (38%) hombres; sólo 39 presentaron ADNS. En el análisis polimórfico de rs104893850 de MSX1 y rs28933373 de PAX9 se obtuvo 94.9% y 84.6% respectivamente de homocigotos mutados. Conclusiones: se obtuvo una alta frecuencia de hipodoncia, el diente que mostró más agenesia fue el órgano dentario 18. Las mutaciones polimórficas están presentes en una alta proporción de agenesia dental (AU)

Introduction: non-syndromic dental agenesis (NSDA) generates negative oral health and psychosocial effects in humans. The genetic determinant plays an important role in its development. Objective: to determine the frequency of MSX1 rs104893850 and PAX9 rs28933373 polymorphisms in patients aged 6 to 18 years with NSDA. Material and methods: prolective cross-sectional study, in which individuals aged 6 to 18 years without congenital defects and from the city of Durango were reviewed. After obtaining their consent to be part of the study, the diagnosis of NSDA was established through a clinical dental inspection, a radiographic examination and a capillary blood sample was taken for the genotyping of the polymorphisms through the qPCR-HRM technique. Results: out of a total of 124 individuals, 77 (62%) females and 47 (38%) males; only 39 presented ADNS. In the polymorphic analysis of rs104893850 of MSX1 and rs28933373 of PAX9 we obtained 94.9% and 84.6% respectively of mutated homozygotes. Conclusions: a high frequency of hypodontia was obtained, and the tooth that presented the most agenesis was dental organ 18. Polymorphic mutations are present in a high proportion for dental agenesis (AU)

O papel de proteínas das vias WNT/ß-Catenina, TGF-ß/BMP4 e SHH na odontogênese e odontomas / The role of proteins from the WNT/ß-Catenin, TGF-ß/BMP4 and SHH pathways in odontogenesis and odontomas

O desenvolvimento do dente depende de uma série de interações sinalizadoras recíprocas entre o epitélio oral (EO) e o ectomesênquima derivado da crista neural, a via WNT com o TGF-ß e BMP4 tem sido implicada na tumorigênese. A via de sinalização tipo Wingless (Wnt) / ß-catenina é essencial para a ativação precoce da odontogênese e no desenvolvimento de tumores odontogênicos. O TGF-ß e as BMPs tem sido associadas aos processos de dentinogênese reacionária e reparadora. A sinalização de Shh pode regular a proliferação celular no ectomesênquima dentário, controlando assim a morfogênese dentária. O objetivo da pesquisa foi investigar a atuação de algumas proteínas das vias na odontogênese e na formação de odontomas e tumores odontogênicos mistos benignos, para isto, foi desenvolvido um estudo seccional restrospectivo e imuno-histoquímico contendo 23 odontomas compostos, 21 odontomas complexos, 17 germes dentários, 05 fibro-odontomas ameloblásticos e 01 fibroma ameloblástico. Os resultados encontrados demonstraram maiores imunoexpressões da via WNT/ß-catenina no epitélio dos germes dentários (p<0,001) e no fibroma ameloblástico, enquanto que, esteve no ectomesênquima dos odontomas (p<0,001) e fibro-odontomas ameloblásticos. A via WNT/ßcatenina correlacionou-se moderadamente e significativamente com a CK14 no epitélio (p = 0,007) dos odontomas. A BMP4 foi imunoexpressa, especialmente, no ectomesênquima dos odontomas complexos (mediana = 33,7; p<0,001). A via Shh foi mais imunoexpressa no epitélio dos germes dentários (p<0,001) e no ectomesênquima dos odontomas complexos (p=0,029). De forma similar, o TGFß apresentou maior imunoexpressão no epitélio dos germes dentários (p<0,001) e no ectomesênquima dos odontomas complexos (p = 0,002). O dente em desenvolvimento exibiu maiores concentrações para estas proteínas no epitélio odontogênico nas fases de botão e capuz e a expressão diferencial ocorreu, principalmente, no ectomesênquima dos tumores, o que indica que esse componente é de fato mais proliferativo (AU).

Tooth development depends on a series of reciprocal signaling interactions between oral epithelium (EO) and neural crest-derived ectomesenchyme, the WNT pathway with TGF-ß and BMP4 has been implicated in tumorigenesis. The Wingless (Wnt)/ß-catenin signaling pathway is essential for the early activation of odontogenesis and the development of odontogenic tumors. TGF-ß and BMPs have been associated with reactionary and reparative dentinogenesis processes. Shh signaling can regulate cell proliferation in dental ectomesenchyme, thus controlling dental morphogenesis. The objective of the research was to investigate the role of some proteins in the pathways in odontogenesis and in the formation of odontomas and benign mixed odontogenic tumors. tooth germs, 05 ameloblastic fibro-odontomas and 01 ameloblastic fibroma. The results found showed higher immunoexpressions of the WNT/ß-catenin pathway in the epithelium of tooth germs (p<0.001) and in ameloblastic fibroma, while it was in the ectomesenchyme of odontomas (p<0.001) and ameloblastic fibroodontomas. The WNT/ß-catenin pathway correlated moderately and significantly with CK14 in the epithelium (p = 0.007) of odontomas. BMP4 was immunoexpressed, especially in the ectomesenchyme of complex odontomas (median = 33.7; p<0.001). The Shh pathway was more immunoexpressed in the epithelium of tooth germs (p<0.001) and in the ectomesenchyme of complex odontomas (p=0.029). Similarly, TGF-ß showed higher immunoexpression in the epithelium of tooth germs (p<0.001) and in the ectomesenchyme of complex odontomas (p = 0.002). The developing tooth exhibited higher concentrations of these proteins in the odontogenic epithelium in the bud and cap phases and the differential expression occurred mainly in the ectomesenchyme of the tumors, which indicates that this component is in fact more proliferative (AU).

Informe de los padres y cuidadores sobre los signos y síntomas de la erupción de los dientes primarios / Relato dos pais e responsáveis sobre sinais e sintomas da irrupção de dentes decíduos / Relato dos pais e responsáveis sobre sinais e sintomas da irrupção de dentes decíduos

La erupción dentaria tiene inicio en las primeras fases de la odontogénesis y termina cuando el diente alcanza su posición funcional en el plano oclusal. La erupción de dientes primarios y la manifestación de los síntomas en niños, es un tema de amplio debate en la literatura. El objetivo del estudio es determinar si se presentan signos y síntomas durante la erupción de los dientes primarios según lo informado por padres y tutores de niños de 6 meses a 3 años. Los datos fueron recolectados a través de un cuestionario dirigido a 50 padres y cuidadores que acompañaban a niños de 6 meses a 3 años para el cuidado odontológico Plataforma Brasil. Hubo signos y síntomas que se describieron como irritabilidad, fiebre, diarrea, encías inflamadas, prurito gingival, salivación excesiva, insomnio, pérdida de apetito, dolor, llanto, estomatitis y sin síntomas reportados. Se puede concluir que la irritabilidad, la fiebre y la diarrea fueron los signos y síntomas más referidos por los padres y tutores.

A irrupção dentária tem início nos primórdios da odontogênese com a fase pré-irruptiva e termina quando o dente atinge a sua posição funcional no plano oclusal. A associação entre irrupção de dentes decíduos e a manifestação de sintomas em crianças é tema de amplo debate na literatura. O objetivo do estudo é determinar se há ocorrência de sinais e sintomas durante a irrupção de dentes decíduos segundo o relato dos pais e responsáveis de crianças de 6 meses a 3 anos de idade. Dados foram coletados através de questionário direcionado a 50 pais e cuidadores que acompanhavam crianças de 6 meses a 3 anos de idade para atendimento odontológico, os dados foram coletados mediante autorização em Termo de Consentimento Livre e Esclarecido e o estudo foi aprovado pelo comitê de ética da Plataforma Brasil. Verificou-se ocorrência de sinais e sintoma que foram descritos como irritabilidade, febre, diarreia, gengiva inchada, coceira gengival, salivação excessiva, insônia, perda de apetite, dor, choro, estomatite e nenhuma sintomatologia relatada. Pode-se concluir que a irritabilidade, febre e diarréia foram os sinais e sintomas mais relatados pelos pais e responsáreis

The dental eruption starts in the early odontogenesis with the pre-irruptive phase and ends when the tooth reaches its functional position in the occlusal plane. The eruption of primary teeth and the manifestation of symptoms in children is the subject of a wide debate in the literature. The purpose of the study is to determine whether signs and symptoms occur during the eruption of deciduous teeth according to the reports of parents and guardians of children aged 6 months to 3 years. Data were collected through a questionnaire directed to 50 parents and caregivers who accompanied children from 6 months to 3 years of age for dental care. Brazil Platform. There were signs and symptoms that were described as irritability, fever, diarrhea, swollen gums, gingival itching, excessive salivation, insomnia, loss of appetite, pain, crying, stomatitis and no reported symptoms. It can be concluded that irritability, fever and diarrhea were the signs and symptoms most reported by parents and guardians

KLF6 facilitates differentiation of odontoblasts through modulating the expression of P21 in vitro / 国际口腔科学杂志·英文版

Multiple signaling pathways are involved in the regulation of cell proliferation and differentiation in odontogenesis and dental tissue renewal, but the details of these mechanisms remain unknown. Here, we investigated the expression patterns of a transcription factor, Krüppel-like factor 6 (KLF6), during the development of murine tooth germ and its function in odontoblastic differentiation. KLF6 was almost ubiquitously expressed in odontoblasts at various stages, and it was co-expressed with P21 (to varying degrees) in mouse dental germ. To determine the function of Klf6, overexpression and knockdown experiments were performed in a mouse dental papilla cell line (iMDP-3). Klf6 functioned as a promoter of odontoblastic differentiation and inhibited the proliferation and cell cycle progression of iMDP-3 through p21 upregulation. Dual-luciferase reporter assay and chromatin immunoprecipitation showed that Klf6 directly activates p21 transcription. Additionally, the in vivo study showed that KLF6 and P21 were also co-expressed in odontoblasts around the reparative dentin. In conclusion, Klf6 regulates the transcriptional activity of p21, thus promoting the cell proliferation to odontoblastic differentiation transition in vitro. This study provides a theoretical basis for odontoblast differentiation and the formation of reparative dentine regeneration.

Temporo-spatial distribution of stem cell markers CD146 and p75NTR during odontogenesis in mice

Abstract Mesenchymal and epithelial stem cells were identified in dental tissues; however, knowledge about the odontogenic stem cells is limited, and there are some questions regarding their temporo-spatial dynamics in tooth development. Objective Our study aimed to analyze the expression of the stem cell markers CD146 and p75NTR during the different stages of odontogenesis. Methodology The groups consisted of 13.5, 15.5, 17.5 days old embryos, and 14 days postnatal BALB/c mice. The expression of CD146 and p75NTR was evaluated by immunohistochemistry. Results Our results showed that positive cells for both markers were present in all stages of tooth development, and the number of positive cells increased with the progression of this process. Cells of epithelial and ectomesenchymal origin were positive for CD146, and the expression of p75NTR was mainly detected in the dental papilla and dental follicle. In the postnatal group, dental pulp cells were positive for CD146, and the reduced enamel epithelium and the oral mucosa epithelium showed immunostaining for p75NTR. Conclusions These results suggest that the staining pattern of CD146 and p75NTR underwent temporal and spatial changes during odontogenesis and both markers were expressed by epithelial and mesenchymal cell types, which is relevant due to the significance of the epithelial-ectomesenchymal interactions in tooth development.

Knockout fth1b affects early mineralization of zebrafish pharyngeal teeth / 华西口腔医学杂志

OBJECTIVES@#A study was conducted to explore the expression pattern and function of ferritin heavy polypeptide gene (fth1b) in zebrafish pharyngeal teeth development and lay the foundation for subsequent research on teeth development and mineralization.@*METHODS@#The zebrafish embryos were harvested at 56, 72, 96, and 120 h after fertilization. The expression of fth1b in zebrafish pharyngeal teeth development was detected by whole embryo @*RESULTS@#The expression pattern of fth1b gene was very similar to that of the known zebrafish pharyngeal teeth marker dlx2b and was specifically expressed in the zebrafish pharyngeal teeth during development. After the specific knockout of the gene fth1b, the earliest gene that can be detect in zebrafish pharyngeal teeth-pitx2 was expressed normally during early development. The dlx2b expression was not significantly different from that of wild type zebrafish, but the mineralization of pharyngeal teeth in the mutant was weaker than that of wild type zebrafish.@*CONCLUSIONS@#The gene fth1b is specifically expressed in zebrafish pharyngeal teeth and acts on their early mineralization.

USP34 regulates tooth root morphogenesis by stabilizing NFIC / 国际口腔科学杂志·英文版

Tooth root morphogenesis involves two biological processes, root elongation and dentinogenesis, which are guaranteed by downgrowth of Hertwig's epithelial root sheath (HERS) and normal odontoblast differentiation. Ubiquitin-dependent protein degradation has been reported to precisely regulate various physiological processes, while its role in tooth development is still elusive. Here we show ubiquitin-specific protease 34 (USP34) plays a pivotal role in root formation. Deletion of Usp34 in dental mesenchymal cells leads to short root anomaly, characterized by truncated roots and thin root dentin. The USP34-deficient dental pulp cells (DPCs) exhibit decreased odontogenic differentiation with downregulation of nuclear factor I/C (NFIC). Overexpression of NFIC partially restores the impaired odontogenic potential of DPCs. These findings indicate that USP34-dependent deubiquitination is critical for root morphogenesis by stabilizing NFIC.

Anomalías dentales en personas con discapacidad / Dental Anomalies in People with Disabilities

RESUMEN Introducción: Durante la odontogénesis se pueden producir malformaciones congénitas que afectan la forma, el número, el tamaño, la estructura, la posición, el color y la erupción de los dientes. En las personas con discapacidades como parálisis cerebral, trastorno del desarrollo intelectual, síndrome de Down y trastorno del espectro autista, pueden presentarse variedad de anomalías dentales. Objetivo: Describir las anomalías dentales en las condiciones de discapacidad de parálisis cerebral, trastorno del desarrollo intelectual, síndrome de Down y trastorno del espectro autista. Métodos: Se realizó una búsqueda bibliográfica en las bases de datos Clinical Key, Medline, Dialnet y SciELO. Se aplicó la lista de comprobación PRISMA. Análisis e integración de la información: Posterior al proceso de lectura y análisis de la información, se recuperaron 800 artículos de las bases de datos, se eliminaron 590 por encontrarse repetidos. Luego de la discriminación, quedaron para revisar 210, a estos restantes se hizo la revisión de texto completo. Se eliminaron 193 no hacían referencia a anomalías dentales y/o a los trastornos o síndromes. De los 17 restantes, solo 15 cumplieron con los criterios de inclusión. Conclusiones: No se encontraron diferencias para afirmar que algunas de las anomalías y alteraciones presentadas correspondan de manera individual a cada tipo de discapacidad. Sin embargo, el síndrome de Down presenta anomalías dentales relacionadas al estado del paciente. La parálisis cerebral reporta otros hallazgos como bruxismo, debido al deficiente desarrollo muscular, lo que afecta la cavidad bucal y sus estructuras(AU)

ABSTRACT Introduction: During odontogenesis, congenital malformations can occur that affect teeth shape, number, size, structure, position, color and eruption. In people with disabilities such as cerebral palsy, intellectual development disorder, Down syndrome, and autism spectrum disorder, a variety of dental abnormalities can occur. Objective: To describe dental anomalies in such disability conditions as cerebral palsy, intellectual development disorder, Down syndrome and autism spectrum disorder. Methods: A bibliographic search was performed in the databases Clinical Key, Medline, Dialnet and SciELO. The PRISMA checklist was applied. Information analysis and integration: After reading and analyzing the information, 800 articles were retrieved from the databases, of which 590 were deleted because they were repeated. After the discrimination, 210 were pending to review; the remaining ones were reviewed full-text. 193 were deleted because they did not do any reference to dental anomalies and/or disorders or syndromes. Of the remaining 17, only 15 met the inclusion criteria. Conclusions: No differences were found to affirm that some of the anomalies and alterations presented correspond individually to each type of disability. However, Down syndrome has dental abnormalities related to patient condition. Cerebral palsy coincides with other findings such as bruxism, due to poor muscle development, which affects the oral cavity and its structures(AU)

COVID-19 Pandemic: Oral Repercussions and its Possible Impact on Oral Health

Abstract Many viral infections cause oral manifestations, including disorders in odontogenesis, resulting in dental malformations. In this review, based on current knowledge, we will discuss the likely dental and oral consequences of COVID-19. In this article, we review currently available data associated with vertical transmission of COVID-19 and odontogenesis, oral manifestations, and the impact of COVID-19 pandemic on a diagnosis of oral diseases. Owing to the severity of the pandemic, the population's anxiety and fear of becoming infected with COVID-19 may underestimate the signs and symptoms of serious illnesses, besides discourage patients from seeking health, medical or dental services to determine the diagnosis of oral lesions. Thus, the COVID-19 pandemic could be an additional and aggravating factor for the delay of serious illness diagnosis, such as oral squamous cell carcinoma resulting in higher morbidity and worse prognosis. Several changes and oral lesions have been described as oral manifestations of COVID-19, such as dysgeusia, oral ulcers, petechiae, reddish macules, desquamative gingivitis, among others. Besides, it can cause major systemic changes and predispose opportunistic infections. As with other viral infections, oral manifestations, including dental anomalies, can occur as a direct result of SARS-CoV-2 infection. However, further studies are needed to guide and clarify possible oral changes.

Low birth weight and the delay on the eruption of deciduous teething in children / Baixo peso ao nascer e atraso na erupção de dentes decíduos em crianças

Abstract Objectives: To analyze the association between low birth weight (LBW) and the occurrence of the delay on the eruption of deciduous teething (DEDT) in children from 04 to 30 months, living in Salvador, Bahia. Methods: A cross-sectional study involved 520 children at four to thirty months of age, from public, private and philanthropic daycares from two districts in Salvador. A descriptive analysis and unconditional logistic regression were done to estimate the odds ratios (ORs), using the Confidence Interval of 95% as a criterion for accepting associations. Poisson regression was used as an analytical strategy to obtain the prevalence ratio. Results: the prevalence of the delay on the eruption was 10.29%. There was a positive association between LBW and occurrence of DEDT among children with less than 24 months, both in the unadjusted model (PR=2.07, 95%CI= 0.96 4.44) as in the adjusted (adjusted PR=2, 27, 95%CI= 1.02 5.07). Conclusions: the variables of development and nutritional at birth and during the early life may be important predictors of the chronology of eruption. Further investigations should be carried out towards the adequate evaluation of the LBW role in the occurrence of the delay on the eruption.

Resumo Objetivos: analisar a associação entre o Baixo Peso ao Nascer (BPN) e a ocorrência de atraso na erupção da dentição decídua (AED) em crianças de 04 a 30 meses, residentes em Salvador-BA. Métodos: estudo transversal envolvendo 520 crianças que frequentavam creches públicas, privadas e filantrópicas de dois Distritos Sanitários de Salvador-Ba. Procedeu-se a análise descritiva e regressão logística não-condicional para estimação da oddsratios (ORs), empregando-se o Intervalo de Confiança a 95% como critério para aceitar as associações. A regressão de Poisson foi utilizada como estratégia analítica para obtenção da Razão de Prevalência. Resultados: a prevalência de atraso na erupção foi de 10,29%. Verificou-se uma associa-ção positiva entre BPN e ocorrência de AED entre as crianças com menos de 24 meses no modelo bruto (RP=2,07, IC95%= 0,96 4,44) e ajustado (RP ajustada=2,27, IC95%= 1,02 5,07). Conclusões: variáveis de desenvolvimento e nutricionais ao nascimento e durante a vida precoce podem ser importantes preditores do tempo de erupção, sendo necessárias outras investigações para uma adequada avaliação desta associação.

Desenvolvimento do sistema estomatognático durante a vida intrauterina: revisão de literatura / Development of the stomatognathic system during the intrauterine life: literature review

Através de uma Revisão da Literatura, o trabalho busca consolidar informações sobre o desenvolvimento do sistema estomatognático, durante a vida intrauterina. Foram realizadas pesquisas sobre o tema abordado, nas seguintes bases de dados: Scielo, Medline; Bireme; Google Acadêmico e o PubMed, no intervalo de tempo de agosto de 2006 a junho de 2017. Livros publicados no mesmo período também foram consultados. Foram selecionados os artigos em português ou inglês, que contemplaram assuntos inerentes ao estudo. O desenvolvimento do sistema estomatognático acontece a partir do primeiro mês gestacional. A exposição materna a fatores de risco como infecções, traumatismos, desnutrição e consumo de drogas, pode deixar sequelas no feto, comprometendo estruturas e funções buco-dentais.

Through a Literature Review, this work aims to consolidate information about the development of the stomatognathic system during the intrauterine life. The development of the stomatognathic system happens from the first gestational month. Maternal exposure to risk factors, such as infections, trauma, malnutrition, drug use, may leave sequels in the fetus and may compromise buccal-dental structures and functions.

Alterações dentárias em crianças com microcefalia associada à Síndrome Congênita do Zika Vírus e outras infecções congênitas / Dental changes in children with microcephaly associated with Congenital Zika Virus Syndrome and other congenital infections

As consequências da microcefalia associada à Síndrome Congênita do Zika Vírus (SCZ) e outras infecções congênitas no desenvolvimento dentário da criança afetada ainda não são bem conhecidas. Os objetivos deste estudo foram avaliar a frequência de alterações dentárias em crianças com microcefalia, analisar se há associação das alterações dentárias com a SCZ e verificar se a microcefalia é fator de risco para as alterações dentárias. Para isso, foram realizados dois estudos observacionais transversais e um estudo do tipo caso-controle. Um único examinador calibrado (Kappa > 0,8) avaliou a presença de alterações dentárias de número, forma e tamanho, alterações na cronologia e sequência de irrupção dentária e alterações no desenvolvimento do esmalte dentário em crianças com microcefalia, associada à SCZ e outras infecções congênitas, e em crianças normoreativas. Informações relacionadas à gestação da mãe e ao nascimento da criança foram coletadas e um questionário socioeconômico foi aplicado. Os dados foram avaliados descritivamente e, como testes de associação, foram utilizados o teste do Qui-quadrado e Exato de Fisher, considerando um nível de significância de 5% (estudos 2 e 3). A amostra do primeiro estudo foi composta por 49 crianças entre 7 e 35 meses de idade apresentando microcefalia associada à SCZ. As alterações mais prevalentes foram as relacionadas à cronologia de irrupção (93,9%; IC95%= 89­99%), às alterações no desenvolvimento do esmalte dentário (76,1%; IC95%= 64­88%) e sequência de irrupção dentária (71,7%; IC95%= 60­84%). No segundo estudo, 62 crianças, com idade entre 7 e 35 meses, portadoras de microcefalia associada à SCZ e outras infecções congênitas compuseram a amostra. Não houve associação estatisticamente significativa entre a SCZ e a presença de alteração na cronologia (p = 1,00) e sequência de irrupção dentária (p = 0,16) e de desenvolvimento do esmalte dentário (p = 1,00). No estudo de caso-controle, 81 crianças entre 30 e 35 meses de idade, normoreativas e portadoras de microcefalia, fizeram parte da amostra, a qual, após identificadas as frequências de cada uma das alterações dentárias, foi emparelhada pelo sexo e idade, na proporção 1:1, e alocadas nos grupos caso (presença de alterações dentárias) e controle (ausência de alterações dentárias). A presença de microcefalia mostrou-se estatisticamente associada ao atraso na irrupção dentária (p < 0,001), à presença de alterações na sequência de irrupção dentária (p < 0,001) e de defeitos no esmalte dentário (p < 0,001). Concluiu-se que as crianças com microcefalia associada à SCZ apresentaram atraso na irrupção dentária, alterações na sequência irruptiva e opacidade do esmalte dos dentes decíduos, no entanto, a infecção pelo vírus Zika não foi associada à ocorrência dessas alterações dentárias. A microcefalia, independente de sua etiologia, é fator de risco para alterações relacionadas ao processo de irrupção dentária e ao desenvolvimento do esmalte dos dentes decíduos (AU).

The consequences of microcephaly associated with Congenital Zika Virus Syndrome (CZS) and other congenital infections on the dental development of the affected child are not well known. The objectives of this study were to evaluate the frequency of dental alterations in children with microcephaly, to analyze if there is an association of dental alterations with CZS, and to verify if microcephaly is a risk factor for dental alterations. For this, two crosssectional observational studies and one case-control study were performed. A single calibrated examiner (Kappa > 0,8) evaluated the presence of dental alterations of number, shape and size, alterations in the chronology and sequence of tooth eruption, and alterations in the tooth enamel development in children with CZS and other congenital infections, as well as in normoreactive children. Information related to mothers' pregnancies and child births were collected and a socioeconomic questionnaire was applied. Data were descriptively evaluated and chi-square test and Fisher's exact test were used as association tests considering a significance level of 5% (studies 2 and 3). The first study sample consisted of 49 children between 7 and 35 months of age with CZS-associated microcephaly. The most prevalent alterations were related to the eruption chronology (93.9%), changes in the development of the enamel (76.1%) and the dental eruption sequence (71.7%). Next, 62 children aged 7 to 35 months with CZS-associated microcephaly and other congenital infections comprised the sample in the second study. There was no statistically significant association between CZS and the presence of changes in chronology (p = 1.00), sequence of tooth eruption (p = 0.16) and tooth enamel development (p = 1.00). In the case-control study, 81 normoreactive children and children with microcephaly between 30 and 35 months of age were part of the sample, which were then paired by gender and age at a 1:1 ratio after identifying the frequencies of each of the dental alterations, and then allocated to the case (presence of dental changes) or control (absence of dental changes) groups. The presence of microcephaly was statistically associated with delayed tooth eruption (p<0.001), the presence of changes in tooth eruption sequence (p<0.001) and dental enamel defects (p<0.001). It was concluded that children with CZS-associated microcephaly had delayed dental eruption, alterations in the eruptive sequence and hypomineralization of primary tooth enamel; however, a Zika virus infection was not associated with these dental changes. A microcephaly, regardless of its etiology, is a risk factor for changes related to the tooth eruption process and the development of primary tooth enamel. It is concluded that microcephaly associated with CZS and other congenital infections is a risk factor for delayed tooth eruption, alterations in the eruptive sequence and defects in dental enamel development occurring (AU).

Effect of grape seed extract (GSE) on functional activity and mineralization of OD-21 and MDPC-23 cell lines

Abstract Recent studies on functional tissue regeneration have focused on substances that favor cell proliferation and differentiation, including the bioactive phenolic compounds present in grape seed extract (GSE). The aim of this investigation was to evaluate the stimulatory potential of GSE in the functional activity of undifferentiated pulp cells and odontoblast-like cells. OD-21 and MDPC-23 cell lines were cultivated in odontogenic medium until subconfluence, seeded in 24-well culture plates in a concentration of 2x104/well and divided into: 1) OD-21 without GSE; 2) OD-21+10 µg/mL of GSE; 3) MDPC-23 without GSE; 4) MDPC-23+10 µg/mL of GSE. Cell proliferation, in situ detection of alkaline phosphatase (ALP) and total protein content were assessed after 3, 7 and 10 days, and mineralization was evaluated after 14 days. The data were analyzed by ANOVA statistical tests set at a 5% level of significance. Results revealed that cell proliferation increased after 10 days, and protein content, after 7 days of culture in MDPC-23 cells. In situ ALP staining intensity was higher in undifferentiated pulp cells and odontoblast-like cells after 7 and 10 days, respectively. A discrete increase in MDPC-23 mineralization after GSE treatment was observed despite OD-21 cells presenting a decrease in mineralized nodule deposits. Data suggest that GSE favors functional activity of differentiated cells more broadly than undifferentiated cells (OD-21). More studies with different concentrations of GSE must be conducted to confirm its benefits to cells regarding dentin regeneration.

Expression patterns of ectodysplasin and ectodysplasin receptor during early dental development in zebrafish / 华西口腔医学杂志

OBJECTIVE@#This study aims to study the expression patterns of ectodysplasin (EDA) and ectodysplasin receptor (EDAR) during the early development of zebrafish and provide a foundation for further research of the Eda signaling pathway in tooth development.@*METHODS@#Total RNA was extracted from zebrafish embryos at 48 hours postfertilization (hpf) and then reverse transcribed for cDNA library generation. The corresponding RNA polymerase was selected for the synthesis of the digoxin-labeled antisense mRNA probe of zebrafish pharyngeal tooth specific marker dlx2b and Eda signaling-associated genes eda and edar in vitro. The three sequences were ligated into a pGEMT vector with a TA cloning kit, and polymerase chain reaction (PCR) was applied to linearize the plasmid. The resultant PCR sequences were used as templates for synthesizing Dig-labeled mRNA probe dlx2b, eda, and edar. Zebrafish embryos were collected at 36, 48, 56, 60, 72, and 84 hpf, then whole mount in situ hybridization was performed for the detection of eda and edar expression patterns. Then, their expression patterns at 72 hpf were compared with the expression pattern of dlx2b.@*RESULTS@#The mRNA antisense probes of dlx2b, eda, and edar were successfully obtained. The positive signals of eda and edar were observed in zebrafish pharyngeal tooth region at 48-72 hpf and thus conform to the signals of dlx2b in the positive regions.@*CONCLUSIONS@#The ligand eda and edar, which are associated with the Eda signaling pathway, are strongly expressed only at the pharyngeal tooth region in zebrafish from tooth initiation to the morphogenesis stage. Thus, the Eda signaling pathway may be involved in the regulation of the early development of zebrafish pharyngeal teeth.

Clinical Risk Factors Influencing Dental Developmental Disturbances in Childhood Cancer Survivors / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although studies regarding dental developmental disturbances after childhood cancer treatment have increased, they have many limitations. Studies analyzing the significance of independent clinical risk factors with regard to the dental health status are also rare. We aimed to investigate the risk factors for dental developmental disturbances, particularly severe disturbances, in childhood cancer survivors (CCS). MATERIALS AND METHODS: Oral examinations and retrospective reviews of medical and panoramic radiographs were performed for 196 CCS (mean age, 15.6 years). Cancer type, age at diagnosis, treatment modality, type and accumulated dose of administered drugs, and dose and site of radiation were recorded. Dental developmental disturbances were diagnosed using panoramic radiographs and graded for severity according to the Modified Dental Defect Index (MDDI). Descriptive statistics and multivariate analyseswere performed to determine the association between dental abnormalities and clinical factors. RESULTS: In total, 109 CCS (55.6%) exhibited at least one dental anomaly, and the median value of MDDI was 2.5. Microdontia (30.6%) was the most prevalent anomaly, followed by tooth agenesis (20.4%), V-shaped roots (14.8%), and taurodontism (10.2%). Multivariate analysis revealed that a young age at diagnosis (≤ 3 years), a history of hematopoietic stem cell transplantation, the use of multiple classes of chemotherapeutic agents (≥ 4 classes), and the use of heavy metal agents were significant risk factors for severe dental disturbances. CONCLUSION: CCS with any of the above risk factors for severe developmental disturbances should be comprehensively followed up to minimize adverse consequences to their dental development and preserve their future dental health.

Induction of Rhesus Keratinocytes into Functional Ameloblasts by Mouse Embryonic Dental Mesenchyme

Fast progresses in stem cell-based tooth tissue engineering have been achieved in recent years in several animal models including the mouse, rat, dog, and pig. Moreover, various postnatal mesenchymal stem cells of dental origin have been isolated and shown capable of differentiating into odontoblasts and generating dentin. Meanwhile, human keratinocyte stem/progenitor cells, gingival epithelial cells, and even iPSC-derived epithelium have been demonstrated to be able to differentiate into functional ameloblasts. Translational medicine studies in the nonhuman primate are irreplaceable steps towards clinical application of stem cell-based tissue engineering therapy. In the present study, we first examined the epithelial stem cell markers in the rhesus skin using immunostaining. Keratinocyte stem cells were then isolated from rhesus epidermis, cultured in vitro, and characterized by epithelial stem cell markers. Epithelial sheets of these cultured keratinocytes, which were recombined with E13.5 mouse dental mesenchyme that possesses odontogenic potential in the presence of exogenous FGF8, were induced to differentiate into enamel-secreting ameloblasts. Our results demonstrate that in the presence of appropriate odontogenic signals, rhesus keratinocytes can be induced to gain odontogenic competence and are capable of participating in odontogenesis, indicating that rhesus keratinocytes are an ideal epithelial cell source for further translational medicine study of tooth tissue engineering in nonhuman primates.

The role of bone morphogenetic protein signaling pathway in tooth root development / 华西口腔医学杂志

The bone morphogenetic protein (BMP) family is an important factor in the regulation of cell ular life activities and in the development of almost all tissues. BMP-mediated signaling plays an important role in tooth root development, which is a part of tooth development. Epithelial and mesenchymal interactions are involved in tooth root development, but the BMP signaling pathway has a different effect on tooth root development in epithelial and mesenchymal. This review summarizes the advances of BMP signaling in tooth root development.