Aspectos clínicos y forenses del color rosa de los dientes: reporte de un caso / Clinical and forensic aspects of the pink color of teeth: report of a case

La coloración rosa de los dientes puede originarse por diferentes factores. En el ámbito forense se ha descrito al fenómeno denominado post mortem pink teeth como un signo asociado a muertes violentas de etiología diversa. En la práctica clínica también es posible observar pacientes con dientes rosados, fre-cuentemente ocasionados por traumatismos o iatro-genia proveniente de ortodoncia, cuyo mecanismo de producción obedece a distintas etiopatogenias, destacándose las reabsorciones dentinarias inter-nas, cemento-dentinarias externas y calcificaciones dentinarias. El presente artículo expone el caso de un individuo adulto con antecedente de trauma óseo-dentario por accidente vial que, luego de un prolon-gado tiempo, asiste al Servicio de Urgencias Odon-tológicas y Orientación de Pacientes de la Facultad de Odontología de la Universidad de Buenos Aires, en donde se le detecta, a modo de hallazgo exploratorio, una ostensible coloración rosada en el canino infe-rior derecho. La situación motivó un pormenorizado abordaje clínico y radiográfico, indagando respecto a los probables factores que intervinieron en su ge-neración y desarrollo (AU)

The pink coloration of the teeth can be caused by dif-ferent factors. In the forensic field, the phenomenon called post mortem pink teeth has been described as a sign associated with violent deaths of various etiology. In clinical practice, it is also possible to ob-serve patients with pink teeth, frequently caused by trauma or iatrogenesis from orthodontics, whose production mechanism is due to different etiopatho-genesis, highlighting internal dentin resorption, ex-ternal cemento-dentinal resorption and dentin calci-fications. This article presents the case of an adult individual with a history of bone-dental trauma due to a road accident who, after a long time, attends the Dental Emergency and Patient Guidance Service of the Faculty of Dentistry of the University of Bue-nos Aires, where an ostensible pink coloration was detected in the lower right canine as an exploratory finding. The situation motivated a detailed clinical and radiographic approach, inquiring about the probable factors that intervened in its generation and development (AU)

Follicle-stimulating hormone impairs dental pulp stem cells odontogenic differentiation.

In addition to bone, the dentin-pulp complex is also influenced by menopause, showing a decreased regenerative capacity. High levels of follicle-stimulating hormone (FSH) during menopause could directly regulate bone metabolism. Here, the role of FSH in the odontogenic differentiation of the dentin-pulp complex was investigated. Dental pulp stem cells (DPSCs) were isolated. CCK-8 assays, cell apoptosis assays, Western blotting (WB), real-time RT-PCR, alkaline phosphatase activity assays, and Alizarin Red S staining were used to clarify the effects of FSH on the proliferation, apoptosis and odontogenic differentiation of the DPSCs. MAPK pathway-related factors were explored by WB assays. FSH and its inhibitor were used in OVX rats combined with a direct pulp-capping model. HE and immunohistochemistry were used to detect reparative dentin formation and related features. The results indicated that FSH significantly decreased the odontogenic differentiation of the DPSCs without affecting cell proliferation and apoptosis. Moreover, FSH significantly activated the JNK signalling pathway, and JNK inhibitor partly rescued the inhibitory effect of FSH on DPSC differentiation. In vivo, FSH treatment attenuated the dentin bridge formation and mineralization-related protein expression in the OVX rats. Our findings indicated that FSH reduced the odontogenic capacity of the DPSCs and was involved in reparative dentinogenesis during menopause.

Relationship between cervical vertebral maturation and dental development in a sample of yemeni children and adolescents / Relación entre la maduración vertebral cervical y el desarrollo dental en una muestra de niños y adolescentes yemeníes

Objective: This study was conducted to investigate the relationship between dental development and cervical vertebral maturation stages in a group of Yemeni children and adolescents. Materials an Methods: The study included digital panoramic radiographs and lateral skull cephalograms obtained from 207 Yemeni subjects­122 females and 85 males aged between 8 to 18 years. Dental maturity was evaluated according to the method of Demirijian et al., calcification stages of the left mandibular canines, first and second premolars and second molars were assessed. Skeletal maturity was assessed by the cervical vertebral maturation (CVM) stages according to the method of Baccetti et al. Correlation between CVM and dental maturation was evaluated by Spearman rank-order correlation coefficient (SROCC). Results: CVM and dental calcification stages were highly correlated (p<0.001) in both genders, ranging from 0.686 to 0.873 for females and 0.787 to 0.871 for males. Calcification stages of the second molars showed the strongest correlation with CVM. Conclusion: Calcification stages of the second molar may be used as a reliable maturation indicator. Dental maturation may be applied to determine the skeletal maturity status of Yemeni children and adolescents.

Objetivo: Este estudio se realizó para investigar la relación entre el desarrollo dental y las etapas de maduración vertebral cervical en un grupo de niños y adolescentes yemeníes. Material y Métodos: El estudio incluyó radiografías panorámicas digitales y cefalogramas laterales del cráneo obtenidos de 207 sujetos yemeníes: 122 mujeres y 85 hombres de entre 8 y 18 años. La madurez dental se evaluó de acuerdo con el método de Demirijian et al. Se evaluaron las etapas de calcificación de los caninos mandibulares izquierdos, primer y segundo premolares y segundos molares. La madurez esquelética se evaluó mediante las etapas de maduración vertebral cervical (CVM) de acuerdo con el método de Baccetti et al. La correlación entre la CVM y la maduración dental se evaluó mediante el coeficiente de correlación de orden de rango de Spearman (SROCC). Resultado: Las etapas de CVM y calcificación dental estuvieron altamente correlacionadas (p<0.001) en ambos sexos, con un rango de 0.686 a 0.873 para las mujeres y 0.787 a 0.871 para los hombres. Las etapas de calcificación de los segundos molares mostraron la correlación más fuerte con CVM. Conclusión: las etapas de calcificación del segundo molar pueden usarse como un indicador de maduración confiable. La maduración dental puede aplicarse para determinar el estado de madurez esquelética de los niños y adolescentes yemeníes.

The spatiotemporal expression and mineralization regulation of p75 neurotrophin receptor in the early tooth development.

OBJECTIVE: The aim of this study was to investigate the spatiotemporal expression and potential role of p75NTR in tooth morphogenesis and tissue mineralization. MATERIALS AND METHODS: The dynamic morphology of the four stages (from the beginning of E12.5 d, then E13.5 d and E15.5 d, to the end of E18.5 d) was observed, and the expressions of p75NTR and Runx2 were traced. The ectomesenchymal stem cells (EMSCs) were harvested in vitro, and the biological characteristics were observed. Moreover, the mineralization capability of EMSCs was evaluated. The relations between p75NTR and ALP, Col-1 and Runx2 were investigated. RESULTS: The morphologic results showed that the dental lamina appeared at E12.5 d, the bud stage at E13.5 d, the cap stage at E15.5 d and the bell stage at E18.5 d. p75NTR and Runx2 showed the similar expression pattern. EMSCs from the four stages showed no significant difference in proliferation. But the positive rate of p75NTR in the E12.5 d cells was significantly lower than that in the other three stages (P < 0.05). Moreover, the higher positive rate of p75NTR the cells were, the stronger mineralization capability they showed. p75NTR was well positively correlated with the mineralization-related markers ALP, Col-1 and Runx2, which increased gradually with the mature of dental germs. CONCLUSION: p75NTR might play an important role in the regulation of tooth morphogenesis, especially dental hard tissue formation.

Assessment of skeletal maturity using the calcification stages of permanent mandibular teeth

Abstract Introduction: Knowledge of the growth status of patients is essential to formulate and initiate a precise treatment plan. This study aimed at determining the role of calcification of permanent mandibular teeth for the assessment of skeletal maturity. Methods: A cross-sectional study was conducted using lateral cephalograms and dental panoramic radiographs of 360 patients (ages 7-18 years) equally divided into six groups according to cervical vertebral maturation stages. Skeletal age was determined using Baccetti et al. method and dental age was calculated using Nolla and Demirjian methods. Results: Mean chronological stage at CS5 revealed a significant difference between male and female subjects (p= 0.003), which showed that the latter achieved skeletal maturity one year earlier than the former. A significant difference (p= 0.007) was found for dental age using Nolla's stages at CS3, which showed females demonstrated a dental age of 1.4 years less than males. Mandibular canine showed the highest correlation with Demirjian index (DI) in males (rho = 0.818) and females (rho = 0.833). Mandibular second premolar showed the highest correlation with Nolla's stages in males (rho = 0.654) and females (rho = 0.664). Conclusion: Comparisons between sexes revealed that females are skeletally and dentally advanced. The DI indicated stage F and Nolla's stages identified stages 9, 10 to be indicative of CS2-3 for the mandibular canine and stages F and G and 9-10 for CS2-3 for the first premolars, second premolars and second molars, respectively.

Resumo Introdução: o conhecimento acerca do status de crescimento dos pacientes é essencial para se formular e iniciar um plano de tratamento preciso. Esse estudo teve como meta determinar a correlação entre a calcificação dos dentes inferiores permanentes e a avaliação da maturação esquelética. Métodos: um estudo transversal foi conduzido utilizando-se radiografias laterais e panorâmicas das arcadas de 360 pacientes (idades entre 7 e 18 anos), igualmente divididos em seis grupos, de acordo com os estágios de maturação esquelética das vértebras cervicais. A idade esquelética foi determinada utilizando-se o método de Baccetti, e a idade dentária foi calculada utilizando-se os métodos de Nolla e Demirjian. Resultados: o estágio cronológico médio em CS5 revelou uma diferença significativa entre os indivíduos do sexo masculino e do feminino (p= 0,003), demonstrando que as meninas alcançavam a maturação esquelética um ano antes dos meninos. Encontrou-se uma diferença significativa (p= 0,007) para a idade dentária utilizando-se os estágios de Nolla em CS3, o que revelou que as meninas exibiam uma idade dentária 1,4 anos inferior à dos meninos. Os caninos inferiores demonstraram a maior correlação com o índice de Demirjian (DI) tanto em indivíduos do sexo masculino (rho = 0,818) quanto do feminino (rho = 0,833). Já os segundos pré-molares inferiores revelaram a maior correlação com os estágios de Nolla, tanto em meninos (rho = 0,654) quanto em meninas (rho = 0,664). Conclusão: as comparações entre os sexos revelaram que as mulheres são mais precoces tanto no desenvolvimento dentário quanto no esquelético. O DI indicou o estágio F, e o método de Nolla identificou os estágios 9 e 10 como indicativos de CS2-3, para os caninos inferiores; e os estágios F e G, e 9 e 10 para CS2-3, para os primeiros e segundos pré-molares, e segundos molares, respectivamente.

Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells.

FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse. Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney. Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner. To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus. The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells. Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression. Consistently, the in vitro mineralization of Fam20c-deficient dental mesenchymal cells was severely disabled. However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism. Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling. In summary, our study discloses that Fam20c indeed regulates cell behaviors and cell signaling pathway in a cell-autonomous manner.

Relationship between dental calcification and skeletal maturation in a Peruvian sample

ABSTRACT Objective: the objective of the study was to determine the relationship between dental calcification stages and skeletal maturation in a Peruvian sample. Methods: panoramic, cephalometric and carpal radiographs of 78 patients (34 girls and 44 boys) between 7 and 17 years old (9.90 ± 2.5 years) were evaluated. Stages of tooth calcification of the mandibular canine, first premolar, second premolar, and second molar and the skeletal maturation with a hand-wrist and a cervical vertebrae method were assessed. The relationships between the stages were assessed using Spearman's correlation coefficient. Additionally, the associations of mandibular and pubertal growth peak stages with tooth calcification were evaluated by Fisher's exact test. Results: all teeth showed positive and statistically significant correlations, the highest correlation was between the mandibular second molar calcification stages with hand-wrist maturation stages (r = 0.758, p < 0.001) and with vertebrae cervical maturation stages (r = 0.605, p < 0.001). The pubertal growth spurt was found in the G stage of calcification of the second mandibular molar, and the mandibular growth peak was found in the F stage of calcification of the second molar. Conclusion: there was a positive relationship between dental calcification stages and skeletal maturation stages by hand-wrist and cervical vertebrae methods in the sample studied. Dental calcification stages of the second mandibular molar showed the highest positive correlation with the hand-wrist and cervical vertebrae stages.

RESUMO Objetivo: o objetivo do presente estudo foi determinar a correlação entre o estágio de calcificação dentária e a maturação esquelética, em uma amostra de indivíduos peruanos. Métodos: radiografias panorâmicas, cefalométricas e carpais de 78 pacientes (34 meninas e 44 meninos) com idades entre 7 e 17 anos (média = 9,90 ± 2,5 anos) foram avaliadas. Nelas, avaliaram-se os estágios de calcificação dentária (canino, primeiro pré-molar, segundo pré-molar e segundo molar inferiores) e de maturação esquelética, pelas avaliações radiográficas da mão e punho e das vértebras cervicais. As correlações entre esses estágios foram avaliadas usando-se o coeficiente de correlação de Spearman. Adicionalmente, a associação entre os estágios em que ocorreram os picos de crescimento mandibular e de crescimento puberal e o grau de calcificação dentária foi avaliada pelo teste exato de Fisher. Resultados: todos os dentes demonstraram correlações positivas e estatisticamente significativas. A correlação mais elevada foi verificada entre o estágio de calcificação do segundo molar inferior e o estágio de maturação esquelética da mão e do punho (r= 0,758, p < 0,001) e o estágio de maturação das vértebras cervicais (r = 0,605, p < 0,001). O surto de crescimento puberal foi identificado no estágio G de calcificação do segundo molar inferior, e o pico de crescimento mandibular foi detectado no estágio F de calcificação do segundo molar. Conclusão: na amostra estudada, houve uma correlação positiva entre os estágios de calcificação dentária e os estágios de maturação esquelética avaliada nas radiografias de mão e punho e das vértebras cervicais. Os estágios de calcificação dentária do segundo molar inferior demonstraram a mais alta correlação positiva com os estágios de maturação da mão e punho e das vértebras cervicais.

Avaliação da mineralização dos segundos molares inferiores como parâmetro para a classificação da idade biológica / Evaluation of the mineralization of permanent second molars as a parameter to classify the biological age of the individual

O presente trabalho teve como objetivo avaliar se a mineralização dos segundos molares inferiores permanentes pode ser usado como parâmetro para classificar a idade biológica do indivíduo. A amostra foi constituída por 129 radiografias panorâmicas, sendo 71 indivíduos do sexo feminino e 58 indivíduos do sexo masculino, na faixa etária de 7 anos à 12 anos e 1 mês. Para a análise da mineralização dental foi utilizada a tabela proposta por Nolla (1960). Os resultados da análise foram documentados numa planilha do programa Microsoft Excel 2010 contendo o nome completo, data de nascimento, data da tomada radiográfica, idade em anos e meses, número do prontuário, estágio de Nolla (1960) lado direito e lado esquerdo. Foi realizada a análise estatística (Mann-Whitney, Wilcoxon e correlação de Spearman) e pôde-se concluir que na amostra estudada não foi encontrado dimorfismo sexual, que a mineralização dentária ocorre de forma similar do lado direito e esquerdo, e que a mineralização dos segundos molares inferiores permanentes podem ser usadas como parâmetro para estimar a idade biológica e cronológica de um indivíduo.(AU)

This paper aimed to evaluate if the mineralization of permanent second molars can be used as a parameter to classify the biological age of the individual. The sample was composed of 129 panoramic radiographs, being 71 females and 58 males, aged 7 years and 12 years and 1 month. For the analysis of dental mineralization it was used a table proposed by Nolla (1960) with X-rays on the negatoscope (light box). The analysis results were documented in a Excel spreadsheet containing the full name, date of birth, date of the radiographic procedure, age in years and months, medical record number, stage of Nolla (1960) right and left side. Performed a statistical analysis, we concluded in our survey that the tooth mineralization occurs similarly in the right and left side, there is a certain precocity when compared to chronological age and the stage of mineralization in females compared to males. We also conclude that within the same chronological age, girls and boys have different mineralization stages, indicating that the dental mineralization can be used to identify the biological age, and the same is poorly correlated with chronological age.(AU)

Dental calcification stages as determinants of the peak growth period.

OBJECTIVE: The objective of this study was to investigate the diagnostic accuracy of dental maturation stages for identifying individual-specific skeletal maturation phases. SUBJECTS AND METHODS: Prior to initiating this study, 255 orthodontic patients comprising 145 girls and 110 boys from the Department of Orthodontics, Aristotle University of Thessaloniki, Greece were identified. Lateral cephalometric and panoramic radiographs were evaluated. Dental calcification stages were assessed according to the Demirjian method and skeletal maturation according to the cervical vertebral maturation stage (CVMS) method. Statistical assessments included Spearman Brown formula, descriptive statistics, Spearman's rho correlation coefficient, and positive likelihood ratios (LHRs). RESULTS: The highest (r = 0.725) correlations were found for second molars and the lowest correlation for canines (r = 0.463, p < 0.001). Positive LHR values exceeding ten were found to identify the pre-peak growth phase in conjunction with the second molar (stage D), second premolar (stage E), and first premolar (stages D and E). Only the second molar (stage F) yielded positive LHR values for identifying the peak growth phase. The positive LHR values for the second molar also facilitated identification of the post-peak growth phase (stage H). Taking the clinical diagnostic efficacy of the second molar into account in identifying these growth phases, we calculated the positive LHRs of the second molar to determine dental maturation stages for diagnosing CVMS II and III. Positive LHR values greater than 10 identified CVMS II (stage D). CONCLUSION: Evaluating dental maturation is a useful initial diagnostic step when assessing skeletal growth. The calcification stages of the second molar provide reliable diagnostic information with which to determine the pubertal growth spurt.

Isolation and Characterization of Human Adult Epithelial Stem Cells from the Periodontal Ligament.

We report a novel method for the isolation of adult human epithelial stem cells (hEpiSCs) from the epithelial component of the periodontal ligament-the human epithelial cell rests of Malassez (hERM). hEpiSC-rich integrin-α6(+ve) hERM cells derived by fluorometry can be clonally expanded, can grow organoids, and express the markers of pluripotency (OCT4, NANOG, SOX2), polycomb protein RING1B, and the hEpiSC supermarker LGR5. They maintain the growth profile of their originating hERM in vitro. Subcutaneous cotransplantation with mesenchymal stem cells from the dental pulp on poly-l-lactic acid scaffolds in nude mice gave rise to perfect heterotopic ossicles in vivo with ultrastructure of dentin, enamel, cementum, and bone. These remarkable fully mineralized ossicles underscore the importance of epithelial-mesenchymal crosstalk in tissue regeneration using human progenitor stem cells, which may have already committed to lineage despite maintaining hallmarks of pluripotency. In addition, we report the clonal expansion and isolation of human LGR5(+ve) cells from the hERM in xeno-free culture conditions. The genetic profile of LGR5(+ve) cells includes both markers of pluripotency and genes important for secretory epithelial and dental epithelial cell differentiation, giving us a first insight into periodontal ligament-derived hEpiSCs.

Composition of mineralizing incisor enamel in cystic fibrosis transmembrane conductance regulator-deficient mice.

Formation of crystals in the enamel space releases protons that need to be buffered to sustain mineral accretion. We hypothesized that apical cystic fibrosis transmembrane conductance regulator (CFTR) in maturation ameloblasts transduces chloride into forming enamel as a critical step to secrete bicarbonates. We tested this by determining the calcium, chloride, and fluoride levels in developing enamel of Cftr-null mice by quantitative electron probe microanalysis. Maturation-stage enamel from Cftr-null mice contained less chloride and calcium than did wild-type enamel, was more acidic when stained with pH dyes ex vivo, and formed no fluorescent modulation bands after in vivo injection of the mice with calcein. To acidify the enamel further we exposed Cftr-null mice to fluoride in drinking water to stimulate proton release during formation of hypermineralized lines. In Cftr-deficient mice, fluoride further lowered enamel calcium without further reducing chloride levels. The data support the view that apical CFTR in maturation ameloblasts tranduces chloride into developing enamel as part of the machinery to buffer protons released during mineral accretion.

MicroRNA-27 promotes the differentiation of odontoblastic cell by targeting APC and activating Wnt/ß-catenin signaling.

MicroRNAs (miRNAs) play an essential role in regulating cell differentiation either by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNAs in odontoblastic cell differentaion is largely unknown. In the present study, we demonstrate that the expression of miR-27 was significantly increased during MDPC-23 odontoblastic cell differentiation. Furthermore, the up-regulation of miR-27 promotes the differentiation of MDPC-23 odontoblastic cells and accelerates mineralization without cell proliferation. In addition, our results of target gene prediction revealed that the mRNA of adenomatous polyposis coli (APC) associated with Wnt/ß-catenin signaling pathway has miR-27 binding site in the its 3' UTR and is suppressed by miR-27. Subsequentially, the down-regulated APC by miR-27 triggered the activation of Wnt/ß-catenin signaling through accumulation of ß-catenin in the nucleus. Our data suggest that miR-27 promotes MDPC-23 odontoblastic cell differentiation by targeting APC and activating Wnt/ß-catenin signaling. Therefore, miR-27 might be considered a critical candidate as an odontoblastic differentiation molecular target for the development of miRNA based therapeutic agents in the dental medicine.

Ion channels, channelopathies, and tooth formation.

The biological functions of ion channels in tooth development vary according to the nature of their gating, the species of ions passing through those gates, the number of gates, localization of channels, tissue expressing the channel, and interactions between cells and microenvironment. Ion channels feature unique and specific ion flux in ameloblasts, odontoblasts, and other tooth-specific cell lineages. Both enamel and dentin have active chemical systems orchestrating a variety of ion exchanges and demineralization and remineralization processes in a stage-dependent manner. An important role for ion channels is to regulate and maintain the calcium and pH homeostasis that are critical for proper enamel and dentin biomineralization. Specific functions of chloride channels, TRPVs, calcium channels, potassium channels, and solute carrier superfamily members in tooth formation have been gradually clarified in recent years. Mutations in these ion channels or transporters often result in disastrous changes in tooth development. The channelopathies of tooth include altered eruption (CLCN7, KCNJ2, TRPV3), root dysplasia (CLCN7, KCNJ2), amelogenesis imperfecta (KCNJ1, CFTR, AE2, CACNA1C, GJA1), dentin dysplasia (CLCN5), small teeth (CACNA1C, GJA1), tooth agenesis (CLCN7), and other impairments. The mechanisms leading to tooth channelopathies are primarily related to pH regulation, calcium homeostasis, or other alterations of the niche for tooth eruption and development.

Information generation and processing systems that regulate periodontal structure and function.

The periodontium is a very dynamic organ that responds rapidly to mechanical and chemical stimuli. It is very complex in that it is composed of two hard tissues (cementum and bone) and two soft connective tissues (periodontal ligament and gingiva). Together these tissues are defined by the molecules expressed by the resident periodontal cells in each compartment and this determines not only the structure and function of the periodontium but also how it responds to infection and inflammation. The biological activity of these molecules is tightly regulated in time and space to preserve tissue homeostasis, influence inflammatory responses and participate in tissue regeneration. In this issue of Periodontology 2000 we explore new experimental approaches and data sets which help to understand the molecules and cells that regulate tissue form and structure in health, disease and regeneration.

Deficiency in acellular cementum and periodontal attachment in bsp null mice.

Bone sialoprotein (BSP) is an extracellular matrix protein found in mineralized tissues of the skeleton and dentition. BSP is multifunctional, affecting cell attachment and signaling through an RGD integrin-binding region, and acting as a positive regulator for mineral precipitation by nucleating hydroxyapatite crystals. BSP is present in cementum, the hard tissue covering the tooth root that anchors periodontal ligament (PDL) attachment. To test our hypothesis that BSP plays an important role in cementogenesis, we analyzed tooth development in a Bsp null ((-/-)) mouse model. Developmental analysis by histology, histochemistry, and SEM revealed a significant reduction in acellular cementum formation on Bsp (-/-) mouse molar and incisor roots, and the cementum deposited appeared hypomineralized. Structural defects in cementum-PDL interfaces in Bsp (-/-) mice caused PDL detachment, likely contributing to the high incidence of incisor malocclusion. Loss of BSP caused progressively disorganized PDL and significantly increased epithelial down-growth with aging. Bsp (-/-) mice displayed extensive root and alveolar bone resorption, mediated by increased RANKL and the presence of osteoclasts. Results collected here suggest that BSP plays a non-redundant role in acellular cementum formation, likely involved in initiating mineralization on the root surface. Through its importance to cementum integrity, BSP is essential for periodontal function.

Preterm infants--odontological aspects.

Preterm birth is associated with medical complications and treatments postnatally and disturbances in growth and development. Primary and permanent teeth develop during this postnatal period. The overall aim of the present thesis was to elucidate the effects of preterm birth and postnatal complications on oral health and the dentoalveolar development during adolescence, and to study the effects of preterm birth on caries during childhood, in a well-defined group of preterm infants. In the same group, explore the development of the primary and permanent teeth and compare the results with a matched control group and control teeth. The subjects consisted of 40 (45) of 56 surviving infants, born < 29 weeks of gestational age (GA), and matched healthy children born at term. The material consisted of 44 teeth from 14 of the preterm adolescents and 36 control teeth from healthy children. Clinical examinations and dental cast analysis were performed during adolescence and morbidity was noted. Retrospective information from medical and dental records was obtained. Dental enamel was analyzed in a polarized light microscopy, and scanning electron microscopy. Further, chemical analyses of enamel and dentin were performed with X-ray microanalysis. The results showed that during adolescence, more preterms had plaque and gingival inflammation, lower salivary secretion, more S. mutans and severe hypomineralization. Retrospectively, less caries was noted at six years of age, but more children had hypomineralization in the primary dentition. Angle Class II malocclusion, large over-bite and deep bite associated with medical diagnoses were frequent. Furthermore, smaller dental arch perimeters in girls, at 16 years of age, and smaller tooth size in the incisors, canines and first molars were found. The morphological findings were confirmed in the XRMA analyses. In postnatal enamel, varying degrees of porosities > 5% and incremental lines were seen. Lower values of Ca and Ca/C ratio and higher values of C were found. Ca/P ratio in both enamel and dentine indicates normal hydroxyapatite in both groups. No single medical diagnosis, postnatal treatment or morbidity in adolescents could explain the findings. As a conclusion, there are indications for poor oral outcome in this group of preterm infants during adolescence, and disturbed mineralization in primary teeth.

Cementomimetics-constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides.

Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides (HABPs) previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 (ADP5) was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein-mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure-function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbidity associated with tooth loss.

Morphogenesis and bone integration of the mouse mandibular third molar.

The mouse third molar (M3) develops postnatally and is thus a unique model for studying the integration of a non-mineralized tooth with mineralized bone. This study assessed the morphogenesis of the mouse M3, related to the alveolar bone, comparing M3 development with that of the first molar (M1), the most common model in odontogenesis. The mandibular M3 was evaluated from initiation to eruption by morphology and by assessing patterns of proliferation, apoptosis, osteoclast distribution, and gene expression. Three-dimensional reconstruction and explant cultures were also used. Initiation of M3 occurred perinatally, as an extension of the second molar (M2) which grew into a region of soft mesenchymal tissue above the M2, still far away from the alveolar bone. The bone-free M3 bud gradually became encapsulated by bone at the cap stage at postnatal day 3. Osteoclasts were first visible at postnatal day 4 when the M3 came into close contact with the bone. The number of osteoclasts increased from postnatal day 8 to postnatal day 12 to form a space for the growing tooth. The M3 had erupted by postnatal day 26. The M3, although smaller than the M1, passed through the same developmental stages over a similar time span but showed differences in initiation and in the timing of bone encapsulation.

Incisor enamel formation is impaired in transgenic rats overexpressing the type III NaPi transporter Slc20a1.

Inorganic phosphate (Pi) is required in many biological processes, including signaling cascades, skeletal development, tooth mineralization, and nucleic acid synthesis. Recently, we showed that Pi transport in osteoblasts, mediated by Slc20a1, a member of the type III sodium-dependent phosphate transporter family, is indispensable for osteoid mineralization in rapidly growing rat bone. In addition, we found that bone mineral density decreased slightly with dysfunction of Pi homeostasis in aged transgenic rats overexpressing mouse Slc20a1 (Slc20a1-Tg). Bone and tooth share certain common molecular features, and thus, we focused on tooth development in Slc20a1-Tg mandibular incisors in order to determine the role of Slc20a1 in tooth mineralization. Around the time of weaning, there were no significant differences in serologic parameters between wild-type and Slc20a1-Tg rats. However, histological analysis showed that Slc20a1-Tg ameloblasts formed clusters in the papillary layer during the maturation stage as early as 4 weeks of age. These pathologies became more severe with age and included the formation of cyst-like or multilayer ameloblast structures, accompanied by a chalky white appearance with abnormal attrition and fracture. Hyperphosphatemia was also observed in aging Slc20a1-Tg rats. Micro-computed tomography and electron probe microanalysis revealed impairments in enamel, such as delayed mineralization and hypomineralization. Our results suggest that enamel formation is sensitive to imbalances in Pit1-mediated cellular function as seen in bone, although these processes are under the control of systemic Pi homeostasis.

The morphology and mineralization of dental hard tissue in the offspring of passive smoking rats.

OBJECTIVE: To study the effects of maternal passive smoking on the morphology and mineralization of dental hard tissue in offspring rats. DESIGN: We have established a maternal passive smoking model. Offspring rats were sacrificed on the 20th day of gestation (E20) or the 3rd (D3) or 10th day (D10) after birth. We observed hard tissue morphology using Haematoxylin-Eosin (H&E) staining sections, used micro computer tomography (Micro-CT) to measure hard tissue thickness and volume on the mandibular first molars of the offspring rats, and used Micro-CT and energy dispersive X-ray spectroscopy with scanning electron microscopy (SEM/EDS) to determine the hard tissue mineral density and the ratio of calcium atom number/calcium atom+phosphorus atom number (Ca(2+)/P(3-)+Ca(2+)). RESULTS: Overall, the development of dental hard tissue was delayed in the offspring of passive smoking rats. The thickness and volume of hard tissue were lower in the offspring of the maternal passive smoking group than in the offspring of the control group. Mineral density of the hard tissue and the ratio of (Ca(2+)/P(3-)+Ca(2+)) were also reduced in the offspring of the maternal passive smoking group. CONCLUSION: Maternal passive smoking inhibits the morphological development and mineralization level of hard tissue on the mandibular first molars of offspring rats.