Examination of the Interproximal Wear Mechanism: Facet Morphology and Surface Texture Analysis.

Dentition is considered a dynamic system with forces that directly affect dental treatment stability and success. Understanding the biomechanical forces that influence tooth alignment is essential for both planning and performing dental treatments, as well as for anthropological and evolutionary studies. While there is currently an abundance of research on the mechanics of dental wear at the occlusal surface, the mechanics of interproximal dental wear is largely unexplored. The fretting mechanism, a wear process resulting from small-amplitude cyclic motion of 2 solid contacting surfaces, was refuted as a possible mechanism for occlusal wear but has never been considered for interproximal wear. Therefore, the aim of the current study was to reveal the biomechanical process of the interproximal wear and to explore whether the fretting mechanism could be associated with this process. Premolar teeth with interproximal wear facets were examined by 3-dimensional surface texture analysis using a high-resolution confocal disc-scanning measuring system. The unique texture topography of 3 areas in the proximal surface of each tooth was analyzed by applying 3D dental surface texture analysis. Each area showed unique texture characteristics, presenting statistically significant differences between the inner area of the facet and its margins or the surface outside the facets borders. Based on these results, we concluded that fretting is a key mechanism involved in interproximal wear.

The association between dental wear and reduced vertical dimension of the face: a morphologic study on human skulls.

OBJECTIVE: The aim of this study was to explore the relationship between dental wear and facial morphology, with particular reference to the occlusal vertical dimension, in modern human skulls. DESIGN: One hundred and three skulls (52 men and 51 women) between the ages of 20 and 50+ years old were studied. The selected skulls were from a modern period (the 17th and the 18th centuries) and included at least one entire condyle and had at least 3 posterior teeth (premolar or molar) in each quadrant to allow for dental articulation. Occlusal wear was evaluated using ordinal scale (0-4) and vertical occlusal dimension was evaluated by measuring upper facial height (UFH), lower facial height (LFH), LFH-to-UFH ratio (L-U-R) and dental wear. Based on the occlusal wear score, two groups were defined: with and without significant wear. RESULTS: Significant relation was observed between age and dental wear (P<0.01). No significant differences were found in the LFH (P=0.847) or UFH (P=0.108) between the two wear groups. In addition, no significant difference (P=0.132) was demonstrated in the LFH-to-UFH ratio between the groups. No difference was observed in the dental wear score between genders (P=0.321). CONCLUSION: Within its limitations, this study demonstrated that dental wear does not influence the vertical dimension of occlusion. Our assumption is that the dento-facial complex fully compensates for the dental effects of wear throughout life.

The onset of p53 loss of heterozygosity is differentially induced in various stem cell types and may involve the loss of either allele.

p53 loss of heterozygosity (p53LOH) is frequently observed in Li-Fraumeni syndrome (LFS) patients who carry a mutant (Mut) p53 germ-line mutation. Here, we focused on elucidating the link between p53LOH and tumor development in stem cells (SCs). Although adult mesenchymal stem cells (MSCs) robustly underwent p53LOH, p53LOH in induced embryonic pluripotent stem cells (iPSCs) was significantly attenuated. Only SCs that underwent p53LOH induced malignant tumors in mice. These results may explain why LFS patients develop normally, yet acquire tumors in adulthood. Surprisingly, an analysis of single-cell sub-clones of iPSCs, MSCs and ex vivo bone marrow (BM) progenitors revealed that p53LOH is a bi-directional process, which may result in either the loss of wild-type (WT) or Mut p53 allele. Interestingly, most BM progenitors underwent Mutp53LOH. Our results suggest that the bi-directional p53LOH process may function as a cell-fate checkpoint. The loss of Mutp53 may be regarded as a DNA repair event leading to genome stability. Indeed, gene expression analysis of the p53LOH process revealed upregulation of a specific chromatin remodeler and a burst of DNA repair genes. However, in the case of loss of WTp53, cells are endowed with uncontrolled growth that promotes cancer.

p53 is required for brown adipogenic differentiation and has a protective role against diet-induced obesity.

Proper regulation of white and brown adipogenic differentiation is important for maintaining an organism's metabolic profile in a homeostatic state. The recent observations showing that the p53 tumor suppressor plays a role in metabolism raise the question of whether it is involved in the regulation of white and brown adipocyte differentiation. By using several in vitro models, representing various stages of white adipocyte differentiation, we found that p53 exerts a suppressive effect on white adipocyte differentiation in both mouse and human cells. Moreover, our in vivo analysis indicated that p53 is implicated in protection against diet-induced obesity. In striking contrast, our data shows that p53 exerts a positive regulatory effect on brown adipocyte differentiation. Abrogation of p53 function in skeletal muscle committed cells reduced their capacity to differentiate into brown adipocytes and histological analysis of brown adipose tissue revealed an impaired morphology in both embryonic and adult p53-null mice. Thus, depending on the specific adipogenic differentiation program, p53 may exert a positive or a negative effect. This cell type dependent regulation reflects an additional modality of p53 in maintaining a homeostatic state, not only in the cell, but also in the organism at large.

p53 counteracts reprogramming by inhibiting mesenchymal-to-epithelial transition.

The process of somatic cell reprogramming is gaining increasing interest as reprogrammed cells are considered to hold a great therapeutic potential. However, with current technologies this process is relatively inefficient. Recent studies reported that inhibition of the p53 tumor suppressor profoundly facilitates reprogramming and attributed this effect to the ability of p53 to restrict proliferation and induce apoptosis. Given that mesenchymal-to-epithelial transition (MET) was recently shown to be necessary for reprogramming of fibroblasts, we investigated whether p53 counteracts reprogramming by affecting MET. We found that p53 restricts MET during the early phases of reprogramming and that this effect is primarily mediated by the ability of p53 to inhibit Klf4-dependent activation of epithelial genes. Moreover, transcriptome analysis revealed a large transcriptional signature enriched with epithelial genes, which is markedly induced by Klf4 exclusively in p53(-/-) cells. We also found that the expression of the epithelial marker E-Cadherin negatively correlates with p53 activity in a variety of mesenchymal cells even before the expression of reprogramming factors. Finally, we demonstrate that the inhibitory effect of p53 on MET is mediated by p21. We conclude that inhibition of the p53-p21 axis predisposes mesenchymal cells to the acquisition of epithelial characteristics and renders them more prone to reprogramming. Our study uncovers a novel mechanism by which p53 restrains reprogramming and highlights the role of p53 in regulating cell plasticity.

Targeted inactivation of Dp71, the major non-muscle product of the DMD gene: differential activity of the Dp71 promoter during development.

The dystrophin gene, which is defective in Duchenne muscular dystrophy (DMD), also encodes a number of smaller products controlled by internal promoters. Dp71, which consists of the two C-terminal domains of dystrophin, is the most abundant product of the gene in non-muscle tissues and is the major product in adult brain. To study the possible function of Dp71 and its expression during development, we specifically inactivated the expression of Dp71 by replacing its first and unique exon and a part of the concomitant intron with a beta-galactosidase reporter gene. X-Gal staining of Dp71-null mouse embryos and tissues revealed a very stage- and cell type-specific activity of the Dp71 promoter during development and during differentiation of various tissues, including the nervous system, eyes, limb buds, lungs, blood vessels, vibrissae and hair follicles. High activity of the Dp71 promoter often seemed to be associated with morphogenic events and terminal differentiation. In some tissues the activity greatly increased towards birth.