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The Wnt pathway is a new target in bone therapeutic space. WNT proteins are potent stem cell activators and pro-osteogenic agents. Here, we gained insights into the molecular and cellular mechanisms responsible for liposome-reconstituted recombinant human WNT3A protein (L-WNT3A) efficacy to treat osteonecrotic defects. Skeletal injuries were coupled with cryoablation to create non-healing osteonecrotic defects in the diaphysis of the murine long bones. To replicate clinical therapy, osteonecrotic defects were treated with autologous bone graft, which were simulated by using bone graft material from syngeneic ACTB-eGFP-expressing mice. Control osteonecrotic defects received autografts alone; test sites received autografts treated ex vivo with L-WNT3A. In vivo µCT monitored healing over time and immunohistochemistry were used to track the fate of donor cells and assess their capacity to repair osteonecrotic defects according to age and WNT activation status. Collectively, analyses demonstrated that cells from the autograft directly contributed to repair of an osteonecrotic lesion, but this contribution diminished as the age of the donor increased. Pre-treating autografts from aged animals with L-WNT3A restored osteogenic capacity to autografts back to levels observed in autografts from young animals. A WNT therapeutic approach may therefore have utility in the treatment of osteonecrosis, especially in aged patients.

Aging is associated with a function decline in tissue homeostasis and tissue repair. Aging is also associated with an increased incidence in osteopenia and osteoporosis, but whether these low bone mass diseases are a risk factor for delayed bone healing still remains controversial. Addressing this question is of direct clinical relevance for dental patients, since most implants are performed in older patients who are at risk of developing low bone mass conditions. The objective of this study was to assess how an osteopenic/osteoporotic phenotype affected the rate of new alveolar bone formation. Using an ovariectomized (OVX) rat model, the rates of tooth extraction socket and osteotomy healing were compared with age-matched controls. Imaging, along with molecular, cellular, and histologic analyses, demonstrated that OVX produced an overt osteoporotic phenotype in long bones, but only a subtle phenotype in alveolar bone. Nonetheless, the OVX group demonstrated significantly slower alveolar bone healing in both the extraction socket, and in the osteotomy produced in a healed extraction site. Most notably, osteotomy site preparation created a dramatically wider zone of dying and dead osteocytes in the OVX group, which was coupled with more extensive bone remodeling and a delay in the differentiation of osteoblasts. Collectively, these analyses demonstrate that the emergence of an osteoporotic phenotype delays new alveolar bone formation.

Objectives: This report aims to describe the development of age-specific phantoms for use in paediatric dentomaxillofacial radiology research. These phantoms are denoted DIMITRA paediatric skull phantoms as these have been primarily developed and validated for the DIMITRA European research project (Dentomaxillofacial paediatric imaging: an investigation towards low-dose radiation induced risks). Methods: To create the DIMITRA paediatric phantoms, six human paediatric skulls with estimated ages ranging between 4 and 10 years- old were selected, protected with non-radiopaque tape and immersed in melted Mix-D soft tissue equivalent material, by means of a careful procedure (layer-by-layer). Mandibles were immersed separately and a Mix-D tongue model was also created. For validation purposes, the resulting paediatric phantoms were scanned using a cone-beam CT unit with different exposure parameter settings. Results: Preliminary images deriving from all scans were evaluated by two dentomaxillofacial radiologists, to check for air bubbles, artefacts and inhomogeneities of the Mix-D and a potential effect on the visualization of the jaw bone. Only skulls presenting perfect alignment of Mix-D surrounding the bone surfaces with adequate and realistic soft tissue thickness density were accepted. Conclusions: The DIMITRA anthropomorphic phantoms can yield clinically equivalent images for optimization studies in dentomaxillofacial research. In addition, the layer-by-layer technique proved to be practical and reproducible, as long as recommendations are carefully followed. The research leading to these results has received funding from the European Atomic Energy Community's Seventh Framework Programme FP7/2007-2011 under grant agreement no 604984 (OPERRA: Open Project for the European Radiation Research Area).

BACKGROUND An increasing number of CBCT units and a wide variability of radiation doses have been reported in dentistry lately. AIM To estimate the effective, cumulative, and organ absorbed doses in children exposed to CBCT over 2 years. DESIGN A prospective study was conducted in children who underwent CBCT diagnostic imaging with the ProMax3D machine. Organ and effective doses were calculated by Monte Carlo simulation using 5- and 8-year-old pediatric voxel phantoms. Extrapolation procedures were applied to estimate doses for other ages and CBCT protocols used in clinical conditions. RESULTS The median effective dose was 137.9 μSv, and the median cumulative dose was 231.4 μSv. Statistically significant differences in the effective doses and cumulative doses were found for various indications of CBCT in children (P < 0.001). The median absorbed organ dose for brain and thyroid was significantly higher for the clinical condition that required large FOVs (2.5 mGy and 1.05 mGy, respectively) compared to medium (0.19 and 0.51 mGy) and small FOVs (0.07 and 0.24 mGy; P < 0.05). The radiation dose of salivary glands did not vary significantly with FOV. CONCLUSION The results revealed the variation of CBCT doses and the influence of FOV size in pediatric exposure.

Autografts tend to be unreliable in older patients. Some of these age-related skeletal changes appear to be attributable to a decline in endogenous WNT signaling. We used a functional in vivo transplantation assay to demonstrate that the bone-forming capacity of an autograft can be traced back to a Wnt-responsive cell population associated with the mineralized bone matrix fraction of a bone graft. Micro-CT imaging, flow cytometry and quantitative analyses demonstrate that this mineralized fraction declines with age, along with a waning in endogenous Wnt signaling; together these factors contribute to the age-related deterioration in autograft efficacy. Using a lipid formulation to stabilize the hydrophobic WNT3A protein, we demonstrate that osteogenic capacity can be restored by incubating the bone graft ex vivo with WNT3A. Compared to control bone grafts, WNT-treated bone grafts give rise to three times more bone. These preclinical results establish a pivotal role for WNT signaling in the age-related decline of autologous bone grafting efficacy, and demonstrate a means to restore that efficacy via local, transient amplification of endogenous Wnt signaling.

Children with unoperated cleft palates have nearly normal growth of their faces whereas patients who have had early surgical repair often exhibit midfacial hypoplasia. Surgical repair is responsible for the underlying bone growth arrest but the mechanisms responsible for these surgical sequelae are poorly understood. We simulated the effect of cleft palate repair by raising a mucoperiosteal flap in the murine palate. Three-dimensional micro-CT reconstructions of the palate along with histomorphometric measurements, finite element (FE) modeling, immunohistochemical analyses, and quantitative RT-PCR were employed to follow the skeletal healing process. Inflammatory bone resorption was observed during the first few days after denudation, which destroyed the midpalatal suture complex. FE modeling was used to predict and map the distribution of strains and their associated stresses in the area of denudation and the magnitude and location of hydrostatic and distortional strains corresponded to sites of skeletal tissue destruction. Once re-epithelialization was complete and wound contracture subsided, the midpalatal suture complex reformed. Despite this, growth at the midpalatal suture was reduced, which led to palatal constriction and a narrowing of the dental arch. Thus the simple act of raising a flap, here mimicked by denuding the mucoperiosteum, was sufficient to cause significant destruction to the midpalatal suture complex. Although the bone and cartilage growth plates were re-established, mediolateral skeletal growth was nonetheless compromised and the injured palate never reached its full growth potential. These data strongly suggest that disruption of suture complexes, which have intrinsic growth potential, should be avoided during surgical correction of congenital anomalies.

Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients.

A new field of dental medicine seeks to exploit nature’s solution for repairing damaged tissues, through the process of regeneration. Most adult mammalian tissues have limited regenerative capacities, but in lower vertebrates, the molecular machinery for regeneration is an elemental part of their genetic makeup. Accumulating data suggest that the molecular pathways responsible for the regenerative capacity of teleosts, amphibians, and reptiles have fallen into disuse in mammals but that they can be “jumpstarted” by the selective activation of key molecules. The Wnt family of secreted proteins constitutes one such critical pathway: Wnt proteins rank among the most potent and ubiquitous stem cell self-renewing factors, with tremendous potential for promoting human tissue regeneration. Wnt reporter and lineage-tracing strains of mice have been employed to create molecular maps of Wnt responsiveness in the craniofacial tissues, and these patterns of Wnt signaling colocalize with stem/progenitor populations in the rodent incisor apex, the dental pulp, the alveolar bone, the periodontal ligament, the cementum, and oral mucosa. The importance of Wnt signaling in both the maintenance and healing of these craniofacial tissues is summarized, and the therapeutic potential of Wnt-based strategies to accelerate healing through activation of endogenous stem cells is highlighted.

The Wnt pathway is a new target in bone therapeutic space. WNT proteins are potent stem cell activators and pro-osteogenic agents. Here, we gained insights into the molecular and cellular mechanisms responsible for liposome-reconstituted recombinant human WNT3A protein (L-WNT3A) efficacy to treat osteonecrotic defects. Skeletal injuries were coupled with cryoablation to create non-healing osteonecrotic defects in the diaphysis of the murine long bones. To replicate clinical therapy, osteonecrotic defects were treated with autologous bone graft, which were simulated by using bone graft material from syngeneic ACTB-eGFP-expressing mice. Control osteonecrotic defects received autografts alone; test sites received autografts treated ex vivo with L-WNT3A. In vivo µCT monitored healing over time and immunohistochemistry were used to track the fate of donor cells and assess their capacity to repair osteonecrotic defects according to age and WNT activation status. Collectively, analyses demonstrated that cells from the autograft directly contributed to repair of an osteonecrotic lesion, but this contribution diminished as the age of the donor increased. Pre-treating autografts from aged animals with L-WNT3A restored osteogenic capacity to autografts back to levels observed in autografts from young animals. A WNT therapeutic approach may therefore have utility in the treatment of osteonecrosis, especially in aged patients.

A variety of clinical classification schemes have been proposed as a means to identify sites in the oral cavity where implant osseointegration is likely to be successful. Most schemes are based on structural characteristics of the bone, for example, the relative proportion of densely compact, homogenous (type I) bone versus more trabeculated, cancellous (type III) bone. None of these schemes, however, consider potential biological characteristics of the bone. Here, we employed multiscale analyses to identify and characterize type I and type III bones in murine jaws. We then combined these analytical tools with in vivo models of osteotomy healing and implant osseointegration to determine if one type of bone healed faster and supported osseointegration better than another. Collectively, these studies revealed a strong positive correlation between bone remodeling rates, mitotic activity, and osteotomy site healing in type III bone and high endogenous Wnt signaling. This positive correlation was strengthened by observations showing that the osteoid matrix that is responsible for implant osseointegration originates from Wnt-responsive cells and their progeny. The potential application of this knowledge to clinical practice is discussed, along with a theory unifying the role that biology and mechanics play in implant osseointegration.

The aim of this study was to assess whether cone beam computed tomography (CBCT) may be used for clinically reliable alveolar bone quality assessment in comparison to its clinical alternatives, multislice computed tomography and the gold standard (micro-CT).Six dentate mandibular bone samples were scanned with seven CBCT devices (ProMax 3D Max, NewTom GiANO, Cranex 3D, 3D Accuitomo 170, Carestream 9300, Scanora 3D, I-CAT Next generation), one micro-CT scanner (SkyScan 1174) and one MSCT machine (Somatom Definition Flash) using two protocols (standard and high-resolution). MSCT and CBCT images were automatically spatially aligned on the micro-CT scan of the corresponding sample. A volume of interest was manually delineated on the micro-CT image and overlaid on the other scanning devices. Alveolar bone structures were automatically extracted using the adaptive thresholding algorithm. Based on the resulting binary images, an automatic 3D morphometric quantification was performed in a CT-Analyser (Bruker, Kontich, Belgium). The reliability and measurement errors were calculated for each modality compared to the gold standard micro-CT.Both MSCT and CBCT were associated with a clinically and statistically (P 0.05) significant measurement error. Bone quantity-related morphometric indices (bone volume fraction 8.41% min to 17.90% max, bone surface density -0.47 mm-1 min to 0.16 mm-1 max and trabecular thickness 0.15 mm min to 0.31 mm max) were significantly (P 0.05) overestimated, resulting in significantly (P 0.05) closer trabecular pores (total porosity percentage -8.41% min to -17.90% max and fractal dimension 0.08 min to 0.17 max) in all scanners compared to micro-CT. However, the structural pattern of the alveolar bone remained similar compared to that of the micro-CT for the ProMax 3D Max, NewTom GiANO, Cranex 3D, 3D Accuitomo 170 and Carestream 9300. On the other hand, the Scanora 3D, i-CAT Next Generation, standard and high-resolution MSCT displayed an overrated bone quantity and aberrant structural pattern compared to other scanning devices. The calculation of morphometric indices had an overall high reliability (intraclass correlation coefficient [ICC] 0.62 min to 0.99 max), except for the i-CAT Next Generation CBCT (ICC 0.26 min to 0.86 max) and standard resolution MSCT (ICC 0.10 min to 0.62 max).This study demonstrated that most CBCT machines may be able to quantitatively assess alveolar bone quality, with a level of accuracy and reliability that approaches micro-CT. One may therefore propose to extrapolate this to clinical CBCT imaging, certainly when there is a need for implant rehabilitation in dentate jaw bones. Conflict-of-interest statement: There is no conflict of interest to declare.Fellowship support was received from Research Foundation Flanders (FWO) from the Belgian government and from the Coordination for the Improvement of Higher Education Personnel (CAPES) programme, Science without Borders, from the Brazilian government.

The aim of this study was to evaluate the effectiveness of metal artefact reduction (MAR) in cone beam CT (CBCT) artefacts arising from metallic objects in the exomass. A radiographic phantom composed of 16 polypropylene tubes filled with a homogeneous radiopaque solution was created. CBCT scans were obtained with two units: Picasso Trio (Vatech, South Korea) and ProMax (Planmeca, Finland). The phantom was centred in a 5 × 5 cm field-of-view (FOV) with titanium and CoCr inserts in the exomass. All scans were repeated after enabling MAR. Mean voxel values were obtained from the 16 tubes and standard deviation was calculated as a way of measuring voxel value variability. Mean values and voxel value variability were compared individually in the presence and absence of MAR by means of analysis of variance, followed by Tukey’s test (α = 0.05). In the Picasso Trio, MAR significantly decreased mean voxel values (p ≤ 0.05) and increased voxel value variability (p > 0.05) in the presence of titanium. When CoCr was present, no statistical difference (p > 0.05) was observed. In the ProMax, MAR increased significantly mean voxel values (p ≤ 0.05) in the presence of titanium, and presented no significant difference (p > 0.05) for CoCr. Voxel value variability did not differ significantly (p > 0.05) for both materials. In conclusion, MAR was not effective to correct CBCT artefacts arising from metallic objects in the exomass in the two CBCT units used.

The preservation of bone viability at an osteotomy site is a critical variable for subsequent implant osseointegration. Recent biomechanical studies evaluating the consequences of site preparation led us to rethink the design of bone-cutting drills, especially those intended for implant site preparation. We present here a novel drill design that is designed to efficiently cut bone at a very low rotational velocity, obviating the need for irrigation as a coolant. The low-speed cutting produces little heat and, consequently, osteocyte viability is maintained. The lack of irrigation, coupled with the unique design of the cutting flutes, channels into the osteotomy autologous bone chips and osseous coagulum that have inherent osteogenic potential. Collectively, these features result in robust, new bone formation at rates significantly faster than those observed with conventional drilling protocols. These preclinical data have practical implications for the clinical preparation of osteotomies and alveolar bone reconstructive surgeries.

Although ultrasonography is a non-invasive, inexpensive and painless diagnostic tool for soft tissue imaging, this technique is not currently used for oral exploration. Therefore, we developed a 25-MHz high-frequency ultrasound probe, specially designed for intraoral applications. This paper aims to present clinical intraoral ultrasound images actually interpretable, in order to identify the relevant applications of this novel tool and to design future oral studies. Two independent radiologists performed ultrasound examinations on three healthy volunteers. All the teeth were explored on the lingual and buccal sides (162 samples) to evaluate the ergonomics of the system and the visualisation of anatomic structures. Osseointegrated dental implants and a mucocele were also scanned. At the gingivodental junction of the maxillary and mandibular teeth, the device clearly identifies the tooth surfaces, the alveolar bone reflection with its surrounding subepithelial connective tissue of the gingiva and the gingival epithelia. The bone level and the thickness of soft tissue around the implant are measurable on the buccal and lingual sides. Therefore, intraoral ultrasonography provides additional morphological information that is not accessible by conventional dental x-rays. We propose a novel diagnostic tool that explores the biological width and is able to define the thin or thick nature of the gums. Moreover, intraoral ultrasonography may help to monitor precancerous lesions. This promising device requires large-scale clinical studies to determine whether it should remain a research tool or be used as a diagnostic tool for daily dental practice.

OBJECTIVES: To assess the influence of artefacts arising from metallic materials in the exomass on cone beam CT (CBCT) voxel values. METHODS: CBCT scans were taken of a phantom composed of 16 tubes filled with a homogeneous hyperdense solution and metallic materials of different compositions (titanium, cobalt–chromium and amalgam) and numbers (one, two and three). The phantom was centred in a 5 × 5 cm field of view such that the metallic materials were located in the exomass, using three CBCT units. Voxel values were obtained from the 16 homogeneous areas and averaged. Also, standard deviation was calculated to measure voxel value variability. Analysis of variance in a factorial scheme with additional treatment 3 × 3 + 3 (material × number + control) was performed, followed by Tukey’s test for multiple comparisons, and Dunnett’s test for comparisons with the control groups, at a level of significance of 5%. RESULTS: Metallic material in the exomass significantly reduced the mean voxel value in the CS9300 and Picasso Trio units, and increased voxel value variability in all CBCT units. Amalgam was the material that induced significantly greater reduction of the mean voxel value in the CS9300 and Picasso Trio units, and significantly greater increase in the NewTom Giano. Voxel value variability was significantly greater for amalgam in all conditions. The presence of one cylinder induced significantly less pronounced effects on the mean voxel value and voxel value variability. CONCLUSIONS: Artefacts arising from metallic materials in the exomass have a negative influence on CBCT voxel values.

Buccal bifurcation cyst is a rare, uncommon buccal cystic lesion associated with the permanent mandibular first molar in children just prior to tooth eruption, and is categorized by the World Health Organization as an odontogenic cyst occurring in a vital tooth, near the buccal cervical margin of the lateral aspect of a root, as a result of an inflammatory process in a periodontal pocket. The aim of this study is to present a series of three similar mandibular buccal bifurcation cyst cases, by providing clinical, radiological and histological characterization of the lesion, in order to lead clinicians through the diagnosis, treatment and follow-up process and contribute to deeper knowledge of this rare pathological entity. ispartof: BJR CASE REPORTS vol:4 issue:2 ispartof: location:England status: published

Resume L’inclusion d’une incisive centrale maxillaire est relativement rare et pose d’autant plus de difficultes au praticien qui la diagnostique. L’etiologie, quand elle est connue, peut etre la presence d’un obstacle a l’eruption ou un traumatisme en denture temporaire. L’incisive centrale incluse est mise en evidence au cours d’un examen de routine ou a la suite d’une inquietude de parents remarquant l’absence d’une dent sur l’arcade. Face a cette anomalie, le praticien doit preciser la situation de la dent incluse et proposer un protocole therapeutique individualise. Quand elle est possible, la mise en place chirurgico-orthodontique est la solution de choix. Dans tous les cas, l’importance des enjeux esthetique et fonctionnel impose aux differents intervenants un choix therapeutique reflechi et une conduite rigoureuse du plan de traitement. Ces differents imperatifs s’inscriront dans une strategie therapeutique pluridisciplinaire adaptee au patient.

Children and teenagers with orthodontics may be affected by infectious, hereditary, traumatic, malignant, or idiopathic oral mucosa lesions. Orthodontists have to be able to detect, identify, and treat effectively or to address the patient to a specialist. Here we discuss this difference to make their diagnosis and management easier for the practitioner.

Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF., info:eu-repo/semantics/published

Mutations in phosphate-regulating gene (PHEX) lead to X-linked hypophosphatemic rickets (XLH), a genetic disease characterized by impaired mineralization in bones and teeth. In human XLH tooth dentin, calcospherites that would normally merge as part of the mineralization process are separated by unmineralized interglobular spaces where fragments of matrix proteins accumulate. Here, we immunolocalized osteopontin (OPN) in human XLH teeth, in a three-dimensional XLH human dental pulp stem cell-collagen scaffold culture model and in a rat tooth injury repair model treated with acidic serine- and aspartate-rich motif peptides (ASARM). In parallel, matrix extracellular phosphoglycoprotein (MEPE) immunolocalization and alkaline phosphatase (ALP) activity were assessed in XLH teeth. OPN was expressed by odontoblasts in the XLH models, and localized to the abnormal calcospherites of XLH tooth dentin. In addition, ALP activity and MEPE localization were abnormal in human XLH teeth, with MEPE showing an accumulation in the unmineralized interglobular spaces in dentin. Furthermore, XLH odontoblasts failed to form a well-polarized odontoblast layer. These data suggest that both MEPE and OPN are involved in impaired tooth mineralization associated with XLH, possibly through different effects on the mineralization process.

Autologous bone grafting represents the standard of care for treating bone defects but this biomaterial is unreliable in older patients. The efficacy of an autograft can be traced back to multipotent stem cells residing within the bone graft. Aging attenuates the viability and function of these stem cells, leading to inconsistent rates of bony union. We show that age-related changes in autograft efficacy are caused by a loss in endogenous Wnt signaling. Blocking this endogenous Wnt signal using Dkk1 abrogates autograft efficacy whereas providing a Wnt signal in the form of liposome-reconstituted WNT3A protein (L-WNT3A) restores bone forming potential to autografts from aged animals. The bioengineered autograft exhibits significantly better survival in the hosting site. Mesenchymal and skeletal stem cell populations in the autograft are activated by L-WNT3A and mitotic activity and osteogenic differentiation are significantly enhanced. In a spinal fusion model, aged autografts treated with L-WNT3A demonstrate superior bone forming capacity compared to the standard of care. Thus, a brief incubation in L-WNT3A reliably improves autologous bone grafting efficacy, which has the potential to significantly improve patient care in the elderly.

Mutations in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) cause X-linked familial hypophosphatemic rickets (XLH), a disorder having severe bone and tooth dentin mineralization defects. The absence of functional PHEX leads to abnormal accumulation of ASARM (acidic serine- and aspartate-rich motif) peptide − a substrate for PHEX and a strong inhibitor of mineralization − derived from MEPE (matrix extracellular phosphoglycoprotein) and other matrix proteins. MEPE-derived ASARM peptide accumulates in tooth dentin of XLH patients where it may impair dentinogenesis. Here, we investigated the effects of ASARM peptides in vitro and in vivo on odontoblast differentiation and matrix mineralization. Dental pulp stem cells from human exfoliated deciduous teeth (SHEDs) were seeded into a 3D collagen scaffold, and induced towards odontogenic differentiation. Cultures were treated with synthetic ASARM peptides (phosphorylated and nonphosphorylated) derived from the human MEPE sequence. Phosphorylated ASARM peptide inhibited SHED differentiation in vitro, with no mineralized nodule formation, decreased odontoblast marker expression, and upregulated MEPE expression. Phosphorylated ASARM peptide implanted in a rat molar pulp injury model impaired reparative dentin formation and mineralization, with increased MEPE immunohistochemical staining. In conclusion, using complementary models to study tooth dentin defects observed in XLH, we demonstrate that the MEPE-derived ASARM peptide inhibits both odontogenic differentiation and matrix mineralization, while increasing MEPE expression. These results contribute to a partial mechanistic explanation of XLH pathogenesis: direct inhibition of mineralization by ASARM peptide leads to the mineralization defects in XLH teeth. This process appears to be positively reinforced by the increased MEPE expression induced by ASARM. The MEPE-ASARM system can therefore be considered as a potential therapeutic target.

L’Autorite de Surete Nucleaire (ASN) definit la radioprotection comme l’« ensemble des regles, des procedures et des moyens de prevention et de surveillance visant a empecher ou a reduire les effets nocifs des rayonnements ionisants produits sur les personnes directement ou indirectement, y compris par les atteintes portees a l’environnement ». Contraignante, la nouvelle reglementation impose a la profession de prendre des mesures de radioprotection strictes et identiques a celles de tous les professionnels exposes aux rayonnements ionisants : • Formation donnees aux professionnels de sante pour la radioprotection des patients, • Designation d’une personne competente en radioprotection, • Mise aux normes des installations avec un controle technique quinquennal, • Mise en place des controles qualite internes, externe et audit. Decoulant du principe d’optimisation, les controles qualite consistent a verifier le maintien des performances de la chaine radiologique permettant l’obtention de cliches de qualite pour un minimum de rayonnements ionisants dans des conditions de securite optimales. La decision de l’Afssaps fixant les modalites du controle qualite des installations de radiologie dentaire a ete publiee au Journal officiel le 26 decembre 2008. La mise en place progressive du controle qualite est prevue en fonction de la date de construction du generateur de rayons X. On distingue : 1. Le controle qualite interne realise par le praticien (ou un prestataire) : il est initial, puis de periodicite trimestrielle pour les techniques numeriques et mensuelle pour les techniques analogiques (argentiques), 2. Le controle qualite externe realise par un organisme de controle agree : il est initial, puis de periodicite quinquennale [avant le 26/12/2009 pour les generateurs de plus de 10 ans (1998), avant le 26/12/2010 pour les generateurs âges de 5 a 10 ans, avant le 26/12/2011 pour les generateurs de moins de 5 ans (2003)], 3. Un audit annuel du controle interne realise par un organisme agree par l’Afssaps (avant le 26/12/2010 et avant 26/12/2012 pour une mise en service apres le 26/12/2009). L’ensemble des operations de controle doit faire l’objet d’une tracabilite. Le praticien doit etablir, tenir a jour et mettre a la disposition de l’organisme de controle de qualite externe, l’inventaire et le registre des operations de maintenance et de controle de qualite. La mise en œuvre pratique du controle qualite interne vise a exposer des « objets test » distincts selon les modalites intra ou extra-orales et selon les dispositifs numeriques ou argentiques. Les images obtenues doivent valider une resolution spatiale et une resolution a bas contraste acceptables (par exemple, au moins 6,3 pl.mm en imagerie intra-orale numerique et 2,5 pl.mm pour une radiographie panoramique). Les fantomes qualite dedies a l’imagerie tridimensionnelle (Cone Beam Computed Tomography) sont en cours de conception et d’evaluation au laboratoire. Les criteres de qualite des images seront specifiques et plus complexes (precision dimensionnelle, restitution des formes selon les plans de coupe, rapport signal/bruit, artefacts...). 56eme Congres de la SFMBCB, 03008 (2011) DOI: 10.1051/sfmbcb/20115603008 © Owned by the authors, published by EDP Sciences, 2011

Severe dental troubles are associated with X-linked hypophosphatemic rickets and are mainly related to impaired dentin mineralization. In dentin matrix, matrix extracellular phosphoglycoprotein (MEPE) may be protected from proteolysis by a specific interaction with PHEX (phosphate regulating gene with homologies to endopeptidases on the X chromosome). The objective of our work was to determine whether PHEX impairment induces MEPE cleavage in dentin and the subsequent release of the C-terminal acidic serine- and aspartate-rich motif (ASARM) peptide, which is known to inhibit mineralization. By Western blot analysis, we explored dentin extracts from seven hypophosphatemic patients with mutations of the PHEX gene. A proteomic approach combining immunoprecipitation, surface-enhanced laser desorption/ionization-time of flight-mass spectrometry and matrix-assisted laser desorption ionization-time of flight analysis of the samples completed this exploration. This study shows a 4.1-kDa peptide containing the MEPE-derived ASARM peptide in hypophosphatemic samples. The presence of ASARM was less marked in patients treated with 1-hydroxylated vitamin D and phosphate during growth. Moreover, recombinant ASARM implanted in a rat pulp injury model disturbed the formation of the reparative dentin bridge. These results suggest that abnormal MEPE cleavage occurs when PHEX activity is deficient in humans, the ASARM peptide may be involved in the mineralization defects and the PHEX-MEPE interaction may be indirect, as ensuring a better phosphate and vitamin D environment to the mineralizing dentin prevents MEPE cleavage.

Impaction of a central maxillary incisor is relatively rare and, consequently, poses all the more problems to the diagnosing practitioner. The etiology, when known, can implicate the presence of an obstacle hindering eruption or a trauma to the temporary dentition. Central incisor impaction is revealed during routine examination or following concern on the part of parents who have noticed that a tooth is missing on the arch. When confronted with this anomaly, the practitioner should determine the precise position of the unerupted tooth and offer a customized treatment protocol. Whenever possible, orthodontic-surgical placement on the arch is the solution of choice. In all cases, the esthetic and functional issues at stake will oblige the various specialists to choose their treatment with caution and to follow the treatment plan very strictly. These different requirements must form part of a customized multidisciplinary treatment strategy.

Digit length ratios, especially the second-to-fourth digit ratio (2D : 4D), are associated with various pathological and behavioural conditions in many species including humans and are dependent upon prenatal androgen to oestrogen balance. It is unknown whether digit ratios are modified by environmental exposure to ubiquitous endocrine disruptors . We studied the effect on adult male Wistar rat digit ratios of a gestational exposure to the oestrogenic and antiandrogenic compounds bisphenol A (BPA), genistein and vinclozolin, in low doses, and in combination with investigating in parallel a possible sexual dimorphism of this trait. We also investigated the effects on the male progeny not exposed during gestation. X-rays were taken of the left and right forepaws, and 2D–5D proximal to distal phalanx distances were measured by a standardized procedure based on semi-automatic image analysis. We provide evidence that there is a sexual dimorphism of digit ratios in the Wistar rat, and we found that BPA alone or in combination with genistein and vinclozolin significantly feminized digit ratios in male rats. Intriguingly, significant feminization of digit ratios was also found in the unexposed male progeny of males that had been exposed to compound mixtures. In conclusion, prenatal environmental levels of endocrine-active substances permanently disrupt digit ratios. Digit ratio measurement in adults is thus a promising biomarker of prenatal exposure to low-dose endocrine disruptors in rodents, with potential implications for future studies in humans.

Certaines tumeurs bénignes des maxillaires se développent dès l'enfance ou au cours de l'adolescence. Il est admis qu'un diagnostic posé précocement permet une meilleure prise en charge et un meilleur pronostic. En plus de l'examen clinique réalisé, l'examen complémentaire est indispensable. Lors de l'examen radiologique, les tumeurs des maxillaires se caractérisent par une image plus ou moins radio-claire. De nouveaux outils permettent une meilleure exploration des tumeurs bénignes des maxillaires, c'est le cas du Cone Beam. Cette thèse a pour but de montrer l'apport du CBCT dans l'exploration des tumeurs bénignes des maxillaires chez l'enfant.

Les traumatismes du secteur antérieur chez l'enfant et l'adolescent représentent des situations d'urgence que le praticien doit prendre en charge le plus rapidement possible, après avoir déterminé un diagnostic positif basé sur des paramètres bien définis. Lors de cette première séance, le praticien délivrera un Certificat Médical Initial, document indispensable pour le suivi du traitement et l'indemnisation. La responsabilité du praticien sera engagée devant toute faute que le patient ou les représentants légaux de ce dernier devront prouver : une anamnèse incomplète, une thérapeutique inadaptée au traumatisme, un mauvais suivi du patient ou un défaut de certificat médical initial. Devant ces paramètres démontrant l'échec de la thérapeutique proposée par le praticien, il reviendra à ce dernier d'expliquer le choix justifié de son traitement et que le préjudice n'est pas de son fait.

Les cavités naso-sinusiennes se trouvent à la frontière de nombreuses disciplines médicales, parmi lesquelles figure l’odontologie. Leur implication dans la pratique dentaire s’explique par leur proximité spatiale avec la cavité orale, rendant fréquente leur visualisation sur nombre d’examens complémentaires pratiqués quotidiennement. Elles peuvent être la source de multiples pathologies développées en leur sein et qu’il est important de prendre en considération, que ce soit du fait de leur pathogénicité intrinsèque ou de leurs répercussions orales éventuelles. Dans la majorité des cas, ces pathologies se présentent au chirurgien-dentiste sous une forme radiographique et fortuite. Cela est d’autant plus vrai que le développement récent de la tomographie volumétrique à faisceau conique (CBCT) s’est accompagné d’une amélioration de la détection des lésions atteignant les régions adjacentes à la cavité orale ainsi que d’une augmentation du nombre d’examens tridimensionnels réalisés par les chirurgiens-dentistes. Ce travail fournit une vision globale des différentes pathologies sinusiennes potentiellement retrouvées sur ces examens CBCT afin de donner un cadre de réflexion au praticien confronté à cette découverte fortuite, afin de l’amener à une prise de décision appropriée.