Bone Marrow Stromal Cells Promote Innervation of Bioengineered Teeth.

Transplantation of bone marrow mesenchymal stem cells (BMDCs) into a denervated side of the spinal cord was reported to be a useful option for axonal regeneration. The innervation of teeth is essential for their function and protection but does not occur spontaneously after injury. Cultured reassociations between dissociated embryonic dental mesenchymal and epithelial cells and implantation lead to a vascularized tooth organ regeneration. However, when reassociations were coimplanted with a trigeminal ganglion (TG), innervation did not occur. On the other hand, reassociations between mixed embryonic dental mesenchymal cells and bone marrow-derived cells isolated from green fluorescent protein (GFP) transgenic mice (BMDCs-GFP) (50/50) with an intact and competent dental epithelium (ED14) were innervated. In the present study, we verified the stemness of isolated BMDCs, confirmed their potential role in the innervation of bioengineered teeth, and analyzed the mechanisms by which this innervation can occur. For that purpose, reassociations between mixed embryonic dental mesenchymal cells and BMDCs-GFP with an intact and competent dental epithelium were cultured and coimplanted subcutaneously with a TG for 2 wk in ICR mice. Axons entered the dental pulp and reached the odontoblast layer. BMDCs-GFP were detected at the base of the tooth, with some being present in the pulp associated with the axons. Thus, while having a very limited contribution in tooth formation, they promoted the innervation of the bioengineered teeth. Using quantitative reverse transcription polymerase chain reaction and immunostainings, BMDCs were shown to promote innervation by 2 mechanisms: 1) via immunomodulation by reducing the number of T lymphocytes (CD3+, CD25+) in the implants and 2) by expressing neurotrophic factors such as NGF, BDNF, and NT3 for axonal growth. This strategy using autologous mesenchymal cells coming from bone marrow could be used to innervate bioengineered teeth without treatment with an immunosuppressor such as cyclosporine A (CsA), thus avoiding multiple side effects.

Dental and extra-oral clinical features in 41 patients with WNT10A gene mutations: A multicentric genotype-phenotype study.

WNT10A gene encodes a canonical wingless pathway signaling molecule involved in cell fate specification as well as morphogenetic patterning of the developing ectoderm, nervous system, skeleton, and tooth. In patients, WNT10A mutations are responsible for ectodermal-derived pathologies including isolated hypo-oligodontia, tricho-odonto-onycho-dermal dysplasia and Schöpf-Schulz-Passarge syndrome (SSPS). Here we describe the dental, ectodermal, and extra-ectodermal phenotypic features of a cohort of 41 patients from 32 unrelated families. Correlations with WNT10A molecular status (heterozygous carrier, compound heterozygous, homozygous) and patient's phenotypes were performed. Mild to severe oligodontia was observed in all patients bearing biallelic WNT10A mutations. However, patients with compound heterozygous mutations presented no significant difference in phenotypes compared with homozygous individuals. Anomalies in tooth morphology were frequently observed with heterozygous patients displaying hypodontia. No signs of SSPS, especially eyelids cysts, were detected in our cohort. Interestingly, extra-ectodermal signs consisted of skeletal, neurological and vascular anomalies, the latter suggesting a wider phenotypic spectrum associated with WNT10A mutations. Indeed, the Wnt pathway plays a crucial role in skeletal development, lipid metabolism, and neurogenesis, potentially explaining patient's clinical manifestations.

Cytokines during periodontal wound healing: potential application for new therapeutic approach.

Regeneration of periodontal tissues is one of the main goals of periodontal therapy. However, current treatment, including surgical approach, use of membrane to allow maturation of all periodontal tissues, or use of enamel matrix derivatives, presents limitations in their indications and outcomes leading to the development of new tissue engineering strategies. Several cytokines are considered as key molecules during periodontal destruction process. However, their role during each phase of periodontal wound healing remains unclear. Control and modulation of the inflammatory response and especially, release of cytokines or activation/inhibition in a time- and spatial-controlled manner may be a potential perspective for periodontal tissue engineering. The aim of this review was to summarize the specific role of several cytokines during periodontal wound healing and the potential therapeutic interest of inflammatory modulation for periodontal regeneration especially related to the expression sequence of cytokines.

Quantification of taurodontism: interests in the early diagnosis of hypohidrotic ectodermal dysplasia.

OBJECTIVE: The aim of this study was to provide a quantification of taurodontism in Hypohidrotic Ectodermal Dysplasia (HED) and to report its occurrence in a cohort of HED patients to assess phenotypic-genotypic correlations. PATIENTS AND METHODS: Of 68 HED patients retrospectively reviewed, 16 patients aged 7-51 years were selected and compared with a control sample (n = 351). The pulp surface index of the first lower permanent molar was calculated from the panoramic radiograph of each individual, and statistical comparisons between the HED patients and the control sample were performed. RESULTS: Whatever the genetic disorder, 81.25% of the HED patients exhibited a relative enlargement (>or=1 s.d.) of the pulp. Major deviations (>5 s.d.) were respectively related to men affected by large deletion of the EDA gene or missense mutation. The autosomal recessive form was linked to a relative moderate pulp enlargement (3.44 s.d.). In NEMO forms, the increase of pulp size in men appeared to be less marked than in EDA mutations. CONCLUSION: This study provides for the first time an objective assessment of pulp enlargement in HED patients, and the various degrees of taurodontism depicted could be interesting dental phenotypic markers of HED forms.

X-linked and autosomal recessive Hypohidrotic Ectodermal Dysplasia: genotypic-dental phenotypic findings.

Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of ectodermal structures and its molecular etiology corresponds to mutations of EDA-EDAR genes. The aim of this study was first to investigate the genotype and dental phenotype associated with HED and second, to explore possible correlations between dental features and molecular defects. A total of 27 patients from 24 unrelated families exhibiting clinical signs of HED (22 XLHED males, 5 autosomal recessive forms) were retrospectively included. In the sample, 25 different mutations on EDA and EDAR genes were detected; 10 were not previously described. EDA and EDAR mutations corresponded respectively to 80.0% and 20.0% of the mutations. The dental phenotype analysis revealed a mean number of primary and permanent missing teeth ranging respectively from 14.5 (4-20) to 22.5 (10-28); the majority of the patients exhibited dysmorphic teeth. Overall, no differential expression in the degree of oligodontia according to either the mutated gene, the mutated functional sub-domains, or the mutation type, could be observed. Nevertheless, the furin group exhibited severe phenotypes unobserved in the TNF group. Significant differences in the number of some primary missing teeth (incisor and canine) related to EDA-EDAR genes defects were detected for the first time between XLHED and autosomal recessive HED, suggesting differential local effects of EDA-EDAR genes during odontogenesis. The present genotypic-phenotypic findings may add to the knowledge of the consequences of the molecular dysfunction of EDA-NF-kB in odontogenesis, and could be helpful in genetic counseling to distinguish autosomal forms from other HED syndromes.

Consequences of X-linked hypohidrotic ectodermal dysplasia for the human jaw bone.

Mutations of the Eda gene, which encodes for ectodysplasin-A1, result in X-linked hypohydrotic ectodermal dysplasia (XLHED). This pathology may lead to severe oligodontia, subsequently requiring implant therapy. Since Eda is suspected to participate in bone development, the jaw bone status was investigated in XLHED patients in order to adjust the surgical protocol. Using computed tomography, densitometric profiles and 3D reconstructions, the bone structure was analyzed and compared to that of control individuals; our results showed that the morphological changes comprised mandibular bone flattening. Craniofacial CT scans showed medullary bone hyperdensity, including in the mandibular symphysis area, where implants must be placed. These alterations in bone structure were also observed in locations where the presence/absence of teeth cannot interfere. If the changes in jaw bone morphology can be a consequence of oligodontia, the changes in bone structure seem to be tooth-independent and suggest a direct effect of the mutation on bone formation and/or remodeling.

Dento-craniofacial phenotypes and underlying molecular mechanisms in hypohidrotic ectodermal dysplasia (HED): a review.

The hypohidrotic ectodermal dysplasias (HED) belong to a large and heterogeneous nosological group of polymalfomative syndromes characterized by dystrophy or agenesis of ectodermal derivatives. Molecular etiologies of HED consist of mutations of the genes involved in the Ectodysplasin (EDA)-NF-kappaB pathway. Besides the classic ectodermal signs, craniofacial and bone manifestations are associated with the phenotypic spectrum of HED. The dental phenotype of HED consists of various degrees of oligodontia with other dental abnormalities, and these are important in the early diagnosis and identification of persons with HED. Phenotypic dental markers of heterozygous females for EDA gene mutation-moderate oligodontia, conical incisors, and delayed dental eruption-are important for individuals giving reliable genetic counseling. Some dental ageneses observed in HED are also encountered in non-syndromic oligodontia. These clinical similarities may reflect possible interactions between homeobox genes implicated in early steps of odontogenesis and the Ectodysplasin (EDA)-NF-kappaB pathway. Craniofacial dysmorphologies and bone structural anomalies are also associated with the phenotypic spectrum of persons with HED patients. The corresponding molecular mechanisms involve altered interactions between the EDA-NF-kappaB pathway and signaling molecules essential in skeletogenic neural crest cell differentiation, migration, and osteoclastic differentiation. Regarding oral treatment of persons with HED, implant-supported prostheses are used with a relatively high implant survival rate. Recently, groundbreaking experimental approaches with recombinant EDA or transgenesis of EDA-A1 were developed from the perspective of systemic treatment and appear very promising. All these clinical observations and molecular data allow for the specification of the craniofacial phenotypic spectrum in HED and provide a better understanding of the mechanisms involved in the pathogenesis of this syndrome.

Contact angle and film pressure: study of a talc surface.

Talc samples in both sheet and powder form are studied by adsorption calorimetry and adsorption isotherm techniques. A model is used to determine the solid surface energy, the solid surface tension and the dispersive, acidic, and basic components of these terms. These results are introduced in an approximate equation relating adsorption to contact angle data. Experimental contact angles are in correct agreement with this approach. The Neumann equation of state is used to fit the data and discussed. It appears as a numerical form of the general equation taking into account gas adsorption and film pressure. Behaviors of talc in contact with liquids do not appear very different whether the solid is in sheet or powder form.

Interactions between Talc Particles and Water and Organic Solvents

Three talc samples have been studied by adsorption and immersion methods after a classical characterization of their properties. The combination of adsorption isotherms and of immersion measurements allows the calculation of enthalpies and entropies of adhesion. The studied talcs are characterized as "middle energy" solids. The differences between the particle shapes of the different samples are shown to be of great importance, indicating a linkage between cristallinity and surface properties. The whole results are explained by the influence of intermolecular forces such as acid-base interactions in the interfacial layer. Copyright 1997 Academic Press. Copyright 1997Academic Press

[Essential hypertension in the child and adolescent. A preliminary study at an interval of more than one year (author's transl)]. / Hypertension artérielle essentielle de l'enfant et de l'adolescent.

One to two years after an initial study establishing normal values for blood pressure in a population of 819 children and adolescents, the outcome in 74 individuals, 39 of whom were considered to be hypertensive and the influence of the observer and methods on the collection of cases of hypertension are evaluated. 58% of the hypertensive individuals remained hypertensive. Overweight appeared to be the essential factor in determining the persistence of hypertension. 74 % of the overweight hypertensive subjects remained hypertensive as against a figure of 42 % of subjects with a normal weight prevent arterial hypertension could be considered by preventing excess weight. The influence of the observer is slight if methods and equipment are identical. Failure to follow the reference methodology increases the number of cases of hypertension artificially. In order to avoid this risk, the practitioner should refer to normographic scales, use the same method and apparatus and repeat measurements yearly or twice a year in order to eliminate observer error.