Céline Gaucher

Bone diseases are increasing with aging populations and it is important to identify clues to develop innovative treatments. Vasn, which encodes vasorin (Vasn), a transmembrane protein involved in the pathophysiology of several organs, is expressed during the development in intramembranous and endochondral ossification zones. Here, we studied the impact of Vasn deletion on the osteoblast and osteoclast dialog through a cell Coculture model. In addition, we explored the bone phenotype of Vasn KO mice, either constitutive or tamoxifen‐inducible, or with an osteoclast‐specific deletion. First, we show that both osteoblasts and osteoclasts express Vasn. Second, we report that, in both KO mouse models but not in osteoclast‐targeted KO mice, Vasn deficiency was associated with an osteopenic bone phenotype, due to an imbalance in favor of osteoclastic resorption. Finally, through the Coculture experiments, we identify a dysregulation of the Wnt/β‐catenin pathway together with an increase in RANKL release by osteoblasts, which led to an enhanced osteoclast activity. This study unravels a direct role of Vasn in bone turnover, introducing a new biomarker or potential therapeutic target for bone pathologies.

BACKGROUND: Objective Structured Clinical Examinations (OSCEs) are amongst the most anxiety‐provoking competency assessment methods. An online serious game (OSCEGame) was developed and implemented within the OSCE curriculum. This study aimed to evaluate the usefulness of this serious game on preparedness and reducing OSCE‐related stress.METHODS: A serious game was designed to help dental students train for OSCEs. Two game courses (4 stations each) were designed according to year of undergraduate training (4^th and 5^th year), based on 6 pre‐existing multi‐competency OSCE stations. The OSCEGame was available online on a learning platform 4 to 6 weeks before the summative OSCEs. Game use was evaluated by analysing connection data. Preparedness, stress and time management skills were assessed using a questionnaire following the summative OCSEs. The results of 4^th‐year students (OSCE naive population) were compared to those of 5^th‐year students to assess usefulness and benefits of such preparation method.RESULTS: In total, 97% and 60% of the students in 4^th year and 5^th year, respectively, used the game. The game was seen as an essential preparation tool to reduce anxiety (for 60% of all students) and increase time management skills (65% of all students). However, significant differences were observed between 4^th− and 5^th‐year students (anxiety reduction: 65% vs. 22%, p < 0.001; time management skills: 59% vs. 41%, p < 0.05) suggesting that it is most useful for OSCE naive students.CONCLUSION: This serious game is a useful time efficient online tool, for OSCE preparation, especially in OSCE naive students.

First described in 1988, vasorin (VASN) is a transmembrane glycoprotein expressed during early mouse development, and with a less extent, in various organs and tissues (e.g., kidney, aorta, and brain) postnatally. Vasn KO mice die after 3 weeks of life from unknown cause(s). No human disease has been associated with variants of this gene so far, but VASN seems to be a potential biomarker for nephropathies and tumorigenesis. Its interactions with the TGF-β and Notch1 pathways offer the most serious assumptions regarding VASN functions. In this review, we will describe current knowledge about this glycoprotein and discuss its implication in various organ pathophysiology.

The importance of phosphate (Pi) as an essential component of hydroxyapatite crystals suggests a key role for membrane proteins controlling Pi uptake during mineralization in the tooth. To clarify the involvement of the currently known Pi transporters (Slc17a1, Slc34a1, Slc34a2, Slc34a3, Slc20a1, Slc20a2, and Xpr1) during tooth development and mineralization, we determined their spatiotemporal expression in murine tooth germs from embryonic day 14.5 to postnatal day 15 and in human dental samples from Nolla stages 6 to 9. Using real-time polymerase chain reaction, in situ hybridization, immunohistochemistry, and X-gal staining, we showed that the expression of Slc17a1, Slc34a1, and Slc34a3 in tooth germs from C57BL/6 mice were very low. In contrast, Slc34a2, Slc20a1, Slc20a2, and Xpr1 were highly expressed, mostly during the postnatal stages. The expression of Slc20a2 was 2- to 10-fold higher than the other transporters. Comparable results were obtained in human tooth germs. In mice, Slc34a2 and Slc20a1 were predominantly expressed in ameloblasts but not odontoblasts, while Slc20a2 was detected neither in ameloblasts nor in odontoblasts. Rather, Slc20a2 was highly expressed in the stratum intermedium and the subodontoblastic cell layer. Although Slc20a2 knockout mice did not show enamel defects, mutant mice showed a disrupted dentin mineralization, displaying unmerged calcospherites at the mineralization front. This latter phenotypical finding raises the possibility that Slc20a2 may play an indirect role in regulating the extracellular Pi availability for mineralizing cells rather than a direct role in mediating Pi transport through mineralizing plasma cell membranes. By documenting the spatiotemporal expression of Pi transporters in the tooth, our data support the possibility that the currently known Pi transporters may be dispensable for the initiation of dental mineralization and may rather be involved later during the tooth mineralization scheme.

In humans, the SOST gene encodes sclerostin, an inhibitor of bone growth and remodeling, which also negatively regulates the bone repair process. Sclerostin has also been implicated in tooth formation, but its potential role in pulp healing remains unknown. The aim of this study was to explore the role of sclerostin in reparative dentinogenesis using Sost knockout mice ( Sost^–/–). The pulps of the first maxillary molars were mechanically exposed in 3-mo-old Sost^–/– and wild-type (WT) mice ( n = 14 mice per group), capped with mineral trioxide aggregate cement, and the cavities were filled with a bonded composite resin. Reparative dentinogenesis was dynamically followed up by micro–computed tomography and characterized by histological analyses. Presurgical analysis revealed a significantly lower pulp volume in Sost^–/– mice compared with WT. At 30 and 49 d postsurgery, a large-forming reparative mineralized bridge, associated with osteopontin-positive mineralization foci, was observed in the Sost^–/– pulps, whereas a much smaller bridge was detected in WT. At the longer time points, the bridge, which was associated with dentin sialoprotein–positive cells, had expanded in both groups but remained significantly larger in Sost^–/– pulps. Sclerostin expression in the healing WT pulps was detected in the cells neighboring the forming dentin bridge. In vitro, mineralization induced by Sost^–/– dental pulp cells (DPCs) was also dramatically enhanced when compared with WT DPCs. These observations were associated with an increased Sost expression in WT cells. Taken together, our data show that sclerostin deficiency hastened reparative dentinogenesis after pulp injury, suggesting that the inhibition of sclerostin may constitute a promising therapeutic strategy for improving the healing of damaged pulps.

Phosphate is a key component of dental mineral composition. The physiological role of membrane proteins of dental cells is suspected to be crucial for mineralization mechanisms. Contrary to published data related to calcium, data on regulation of phosphate flux through membrane of mineralizing cells are scarce. To address this lack of data, we studied the expression of six membranous phosphate transporters in two dental cell lines: a rat odontoblastic cell line (M2H4) and a mouse ameloblastic cell line (ALC) for which we optimized the mineralizing culture conditions.

Epidemiological data on dental caries show that prevention and treatment needs have evolved significantly over the past two decades. In younger patients the distribution of caries lesions is mainly found on the occlusal surfaces. The treatment approaches utilised by dentists must evolve to integrate preventive and treatment solutions tailored to the care needs, which are straightforward to implement in the dental office and whose effectiveness is underpinned by scientific evidence. This article aims to describe the principles of non-invasive management of non-cavitated (initial) occlusal caries lesions, based on evidence from recent studies published in the international literature.

The detection of carious lesions is focused on the identification of early mineral changes to allow the demineralisation process to be managed by non-invasive interventions. The methods recommended for clinical diagnosis of initial carious lesions are discussed and illustrated. These include the early detection of lesions, evaluation of the extent of the lesion and its state of activity and the establishment of appropriate monitoring. The place of modern tools, including those based on fluorescence, is discussed. These can help inform patients. They are also potentially useful in regular control visits to monitor the progression or regression of early lesions. A rigorous and systematic approach to caries diagnosis is essential to establish a care plan for the disease and to identify preventive measures based on more precise diagnosis and to reduce reliance on restorative measures.