Concise Review: Cellular and Molecular Mechanisms Regulation of Tooth Initiation.

Development of teeth depends on the reciprocal interactions between the surface epithelium (ectoderm) and the underlying neural crest-derived mesenchyme. These interactions are facilitated by the conserved signaling pathways, which build a complex network of signals and transcription factors. Tooth development starts at specific and predetermined loci in the oral ectoderm and is described as a morphologically distinct thickening of oral ectoderm, named dental lamina. Cells within the dental lamina invaginate into the underlying mesenchyme, generating placodes that mark the onset of individual tooth development. In the following stages of development, the tooth epithelium buds and folds transitioning through various shapes, including bud, cap, and bell shapes, which also identify the specific stages of tooth development. Although much of the molecular regulation of tooth development has been unraveled, the regulation of the initial stages of tooth development, as well as the cellular mechanisms that govern tooth development remain largely unknown. This review provides a systematic overview of the current knowledge on the molecular and cellular mechanisms that guide initial stages of tooth development and outlines the challenges which temper the progress. Stem Cells 2019;37:26-32.

Immunomodulatory Effect of Cytokines in the Differentiation of Mesenchymal Stem Cells: A Review.

Mesenchymal stem cells (MSCs) are stromal origin cells with multilineage differentiation capacity. The immunoregulatory properties of MSCs can be interfered effectively by cytokines. Cytokines, produced by a broad range of cells, act at the systemic level to influence biological phenomena such as inflammation, wound healing, organogenesis and oncogenesis. Cytokines also play vital roles in the differentiation of MSCs into several cell lineages. This review summarizes on how cytokines can affect MSCs differentiation and their relative signaling pathways, which may serve to understand the possible underlying mechanisms. Also, this review reveals the potential clinical use of MSCs as promising therapeutic agents due to their special characteristics such as multipotent differentiation, immunomodulatory properties, and selfrestoration.

Imunoexpressão das claudinas -1 e -7 em ameloblastomas e germes dentais humanos / Imunoexpressão of the claudinas -1 and -7 in ameloblastomas and human dental embryos

Investigamos a expressão imuno-histoquímica das claudinas -1 e -7 em ameloblastomas e germes dentais humanos, avaliando o padrão de distribuição (focal, regional ou difuso), as células que as expressam (central ou periférica) e a localização dessa expressão nos constituintes celulares considerando membrana, citoplasma e núcleo. Dentre os 29 casos de ameblastomas, 23 eram do tipo sólido e 6 unicísticos. Nos 7 espécimes mandibulares de fetos humanos observamos germes dentais foi variável para as claudinas estudadas de acordo com o tipo celular e estágio de diferenciação assemelhando-se apenas nas células do retículo estrelado. No epitélio interno a expressão da claudina-1 foi decrescente com a progressão da diferenciação enquanto para a claudina-7 foi verificada nas células periféricas da papila. Para os ameloblastomas, de forma geral, a expressão foi mais significativa do que aquela observada nos germes dentais. Foi aplicado o teste estatístico de Fischer o qual não demonstrou associação entre a expressão das claudinas nas células centrais e periféricas e o tipo do ameloblastoma (sólido ou unicístico)...

Novel intraoral phenotypes in hyperimmunoglobulin-E syndrome.

AIM: Hyperimmunoglobulin-E syndrome (HIES) is a primary immunodeficiency characterized by eczema, recurrent skin and lung infections with pneumatocoele formation, and extremely elevated serum immunoglobulin-E. The precise immunologic defect and genetic etiology remain unknown. Non-immunologic findings include characteristic facial features (prominent forehead, fleshy nasal tip, and increased interalar distance); skeletal involvement (pathological fractures, scoliosis, and craniosynostosis); and retention of primary teeth. This study aims to characterize intraoral soft tissue findings in HIES patients. METHODS: Sixty HIES patients (4-54 years, 27 males, 33 females) received intraoral and radiographic evaluations. Chronological dental development was also assessed. RESULTS: Lesions of the hard palate and dorsal tongue were found in 55% and 60% of patients, respectively. Palatal lesions ranged from a generalized surface keratosis to a midline sagittal fibrotic bridge. Tongue lesions consisted of multiple fissures and a midline cleft. On the lip and buccal mucosa, keratotic plaques and/or surface fissures were found in 8% and 23% of patients, respectively. Manifested in 76.7% of patients, the intraoral lesions were significantly more prevalent than the characteristic facial traits (P=0.0013). CONCLUSIONS: Alterations in oral mucosa and gingiva were present in the majority of HIES patients. These novel intraoral findings may facilitate the diagnosis of HIES.

Different distribution of immunocompetent cells in the dentogingival junction during root formation in rat molars.

The distribution of immunocompetent cells in the dentogingival junction of rat molars during root formation was investigated by immunocytochemistry using antibodies to class II major histocompatibility complex (MHC) molecules (OX6-antibody) and monocyte/macrophage lineage cells (ED1-antibody) as well as by histochemical reaction for periodic acid-Schiff (PAS). Two portions (the junctional epithelium in the mesial gingiva of the first molar, and the interdental gingiva between the first and second molars) were selected for observations. At the eruption stage of the first molar (16-18 days after birth), OX6-positive cells, dendritic or oval in shape, were abundantly distributed in the connective tissue between the oral epithelium and tooth germ. Positive cells with slender cell processes were also found beneath the ameloblast layer. At the commencement stage of the first molar occlusion (24-28 days after birth), numerous OX6-positive cells displaying a dendritic fashion existed preferentially in the mesial gingiva, but were fewer in the interdental gingiva. In contrast, the interdental gingiva showed a denser distribution of ED1-positive cells and PAS-reactive polymorphonuclear leukocytes (PMLs) than the mesial gingiva. At the completion stage of root formation (100-120 days after birth), the OX6-immunopositive cells invaded the deeper position of the mesial gingiva with the downgrowth of the epithelium; they had a considerably higher cell density compared with those in the interdental gingiva where PAS-reactive PMLs persisted. These findings indicated that the immunocompetent cells showed a region-specific distribution and cell density by their roles in immune response.

Characterization of novel monoclonal antibodies raised against formalin-fixed, paraffin-embedded human ameloblastoma.

To obtain monoclonal antibodies reactive with odontogenic but not other types of epithelium, mice were immunized with homogenates of fixed ameloblastoma tissues, and monoclonal antibodies Y4 and M11 were produced. Y4 reacted immunohistochemically with odontogenic epithelial components but not with those of squamous differentiation, while M11 reacted with odontogenic epithelial components and a part of keratotic epithelial tissues. Immunoglobulin isotypes of both antibodies were IgM as determined by Ouchterlony immunodiffusion and enzyme-linked immunosorbent assays. Western blotting revealed that the antigen recognized by Y4 had a molecular mass of approximately 66 kDa; however, the antigen reactive with M11 was not identified by Western blotting in spite of various attempts in changing reaction conditions. These antibodies may be beneficial to histological analyses of odontogenic tissues and their related lesions.

Age-related changes in the immunoreactivity of the monocyte/macrophage system in rat molar pulp.

Defence reactions of the dental pulp potentially involve a variety of immunocompetent cells, particularly class II major histocompatibility complex (MHC)-expressing cells and macrophages. In order to examine how the immunodefence potential of the pulp changes as a function of age, phenotypic distribution of pulpal cells expressing immunoreactivity to monoclonal antibody ED1 (reactive with nearly all macrophages and dendritic cells) was examined immunohistochemically in the lower first molars of developing (new-born to 10-week-old), adult (14-24-week-old) and aged (1-1.5-yr-old) Wistar rats. During tooth development, increasing numbers of ED1+ cells in the pulp also expressed immunoreactivity to ED2 (reactive with a differentiation-related antigen present on resident macrophages). ED1+ and ED2+ cells were distributed throughout the pulp before the tooth formation was completed. OX6+ (class II MHC-expressing) cells started to increase in number shortly after the eruption of the tooth and the increase continued even after the tooth formation had been completed. In aged rats, the density of the pulpal ED1+ cells was maintained at a relatively high level, whereas a significant decrease in the density of OX6+ cells was observed. These results indicate that the density and composition of pulpal cells expressing macrophage-associated antigens vary with increasing age, which most probably is related to changes in the immunological defence potential of the pulp against infection.

Efeitos da desidratação sobre o crescimento dentário em ratos adrenalectomizados / Dehydration effects on the dental growth in adrenalectomized rats

Aproveitando o crescimento contínuo de dentes em ratos neste trabalho foram verificados os efeitos das variações nutricionais e hormonais sobre os mecanismos que atuam na odontogênese. Para tanto, observou-se o efeito da desidratação sobre o crescimento dentário em ratos adrenalectomizados, submetidos à alteração da fotoperiodicidade, utilizando-se 55 ratos albinos machos, com idades entre 60 e 80 dias, divididos em quatro grupos: IC (animais mantidos em iluminação contínua); IC + D (animais mantidos em iluminação contínua e privados da ingestão de líquidos por 6 dias); IC + A (submetidos à iluminação contínua e adrenalectomia) ; IC + A + D (submetidos à iluminação contínua, adrenalectomia e desidratação). Os controles foram feitos nos períodos de 1, 3, 6, 7, 9, 12 e 15 dias. Foi verificado que a média diária de crescimento dentário no grupo IC foi 0,41± 0,02 mm; do grupo IC + D foi 0,35 + 0,01 mm (p<0,01), do grupo IC + A 0,36 ± 0,02 mm (p<0,01) e do grupo IC + A + D 0,28 ± 0,01 mm (p<0,01). Os resultados obtidos permitem concluir: 1) A desidratação promove diminuição do rítmo de crescimento dentário; 2) A alteração é mais evidente com a intensificação da desidratação; 3) A adrenalectomia induz à redução do crescimento do dente; 4) A alteração é maior nos animais adrenalectomizados submetidos à desidratação

A chondroitin sulfate epitope in mammalian dental pulp and its developmental expression in mouse dental papilla.

The molecular specificity of the dental papilla of a bell-stage tooth was studied by production of dental-papilla-reactive monoclonal antibodies (Mabs). One of the Mabs, designated 7C5, recognized an epitope present in glycosaminoglycan. Several lines of evidence suggested that the 7C5-epitope consists of chondroitin 6-sulfate. The Mab did not react with mouse dental epithelium, but reacted uniformly with mesenchymal tissue in the mandibular process and accumulated in the dental sac and in the papilla of bell-stage tooth germs. The 7C5-staining was lost from the differentiating odontoblasts, while the staining in the molar tooth papilla was accumulated in the subodontoblastic layer. In the developing mouse incisor, the 7C5-epitope was restricted to the lingual-posterior area. The 7C5-epitope was also present in pulpal tissue and predentin of different types of teeth of various mammalian species, including man, sheep, swine, and rat. Collagenase pre-treatment of tissue sections abolished the bulk of the 7C5-reactivity in peridental mesenchyme during embryonic stages while leaving the staining of the dental papilla intact. In newborn and adult teeth, collagenase also impaired the reactivity in the pulp except for the subodontoblastic layer. This suggests the existence of different subpopulations of the 7C5-epitope containing proteoglycans in dental papilla and pulp. A high-molecular-weight proteoglycan, sensitive to chondroitinase ABC but not to heparinase or heparitinase, was immunoprecipitated by 7C5 from extracts of bell-stage mouse tooth germs. We suggest that the evolutionary conservation of chondroitin 6-sulfate in the dental pulp reflects its properties as non-terminally differentiated tissue and perhaps the retention of a potential to differentiate to odontoblasts.