New finite element study protocol: Clinical simulation of orthodontic tooth movement.

The aim of this work was to model tooth movement in a more clinically-exact fashion, thanks to the use of new IT tools and imaging systems (cone-beam). Image segmentation and 3D reconstruction now enable us to model the anatomy realistically, while finite element (FE) analysis makes it possible to evaluate stresses and their distribution on the level of the tooth, the periodontal ligament (PDL) and the alveolar bone when a force is applied. The principle is to monitor tooth movement by obtaining optical impressions at each stage of treatment. The model corresponds to a genuine clinical situation. FE analysis is correlated with the clinically-observed displacement. The protocol remains long and complex. It nevertheless makes it possible to obtain, throughout the duration of treatment, patient-specific models that can be exploited using finite element methods. It requires further validation in more thorough studies but offers interesting prospects: precise study of induced tooth movement, distribution of stresses in the PDL, and development of a customized previsualization tool.

Role of RANKL (TNFSF11)-dependent osteopetrosis in the dental phenotype of Msx2 null mutant mice.

The MSX2 homeoprotein is implicated in all aspects of craniofacial skeletal development. During postnatal growth, MSX2 is expressed in all cells involved in mineralized tissue formation and plays a role in their differentiation and function. Msx2 null (Msx2 (-/-)) mice display complex craniofacial skeleton abnormalities with bone and tooth defects. A moderate form osteopetrotic phenotype is observed, along with decreased expression of RANKL (TNFSF11), the main osteoclast-differentiating factor. In order to elucidate the role of such an osteopetrosis in the Msx2 (-/-) mouse dental phenotype, a bone resorption rescue was performed by mating Msx2 (-/-) mice with a transgenic mouse line overexpressing Rank (Tnfrsf11a). Msx2 (-/-) Rank(Tg) mice had significant improvement in the molar phenotype, while incisor epithelium defects were exacerbated in the enamel area, with formation of massive osteolytic tumors. Although compensation for RANKL loss of function could have potential as a therapy for osteopetrosis, but in Msx2 (-/-) mice, this approach via RANK overexpression in monocyte-derived lineages, amplified latent epithelial tumor development in the peculiar continuously growing incisor.

Bone resorption control of tooth eruption and root morphogenesis: Involvement of the receptor activator of NF-κB (RANK).

Activation of the receptor activator of NF-κB (RANK) is a crucial step in osteoclastogenesis. Loss- and gain-of-function mutations in the Rank gene cause, respectively, osteopetrosis and several forms of extensive osteolysis. Tooth and alveolar bone alterations are associated with these pathologies but remain to be better characterized. The aim of the present study was to establish the tooth and alveolar bone phenotype of a transgenic mouse model of RANK over-expression in osteoclast precursors. Early tooth eruption and accelerated tooth root elongation were observed subsequent to an increase in osteoclast numbers surrounding the tooth. The final root length appeared not to be affected by RANK over-expression, but a significant reduction in root diameter occurred in both control and root-morphogenesis-defective Msx2 null mutant mice. These results indicate that root length is independent of the surrounding bone resorption activity. In contrast, root diameter is sensitive to the activity of alveolar bone osteoclasts. These data suggest that early eruption and thin root are phenotypic features that could be associated with extensive osteolytic pathologies.

Enamel protein regulation and dental and periodontal physiopathology in MSX2 mutant mice.

Signaling pathways that underlie postnatal dental and periodontal physiopathology are less studied than those of early tooth development. Members of the muscle segment homeobox gene (Msx) family encode homeoproteins that show functional redundancy during development and are known to be involved in epithelial-mesenchymal interactions that lead to crown morphogenesis and ameloblast cell differentiation. This study analyzed the MSX2 protein during mouse postnatal growth as well as in the adult. The analysis focused on enamel and periodontal defects and enamel proteins in Msx2-null mutant mice. In the epithelial lifecycle, the levels of MSX2 expression and enamel protein secretion were inversely related. Msx2+/- mice showed increased amelogenin expression, enamel thickness, and rod size. Msx2-/- mice displayed compound phenotypic characteristics of enamel defects, related to both enamel-specific gene mutations (amelogenin and enamelin) in isolated amelogenesis imperfecta, and cell-cell junction elements (laminin 5 and cytokeratin 5) in other syndromes. These effects were also related to ameloblast disappearance, which differed between incisors and molars. In Msx2-/- roots, Malassez cells formed giant islands that overexpressed amelogenin and ameloblastin that grew over months. Aberrant expression of enamel proteins is proposed to underlie the regional osteopetrosis and hyperproduction of cellular cementum. These enamel and periodontal phenotypes of Msx2 mutants constitute the first case report of structural and signaling defects associated with enamel protein overexpression in a postnatal context.

[Known gene interactions as implicated in craniofacial development]. / Ensemble des gènes connus comme impliques dans le développement cranio-facial.

Many genes intervening in development, morphogenesis and craniofacial growth have been identified, primarily by the use of mice mutants. We can distinguish two families: the signalling factors and the transcription factors. The latter interact with DNA to activate or to inhibit the expression of other genes. Some of the transcription factors are called homeogenes because they interact with DNA by a sequence of amino acids known as homeobox that has been carefully conserved throughout the course of evolution. Those factors interact, and signalling cascades have been described. Current research projects seek to discern the exact role of each of these genes in craniofacial growth and to develop a better understanding of the interactions between them.

[Twins and the heritability of dentofacial phenotype]. / Jumeaux et héritabilité des phénotypes dento-faciaux.

In orthodontics and dentofacial orthopaedics, where genetic and environmental factors interpenetrate from the early stages of development, the clinician tries to determine how mechanics could influence patient's growth pattern. Comparing monozygotic and dizygotic twins, in their similarities and their differences, gives some answers... but raises some questions too. In this article, we gather some clinical studies and case reports, on diagnosis and treatment aspects of malocclusions.