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AIM The purpose of this study was to evaluate force systems to bring about the en masse retraction of maxillary anterior teeth having reduced bone levels using finite element analysis. MATERIALS AND METHODS This is a prospective study. Three-dimensional finite element models of maxillary dentition having normal alveolar bone level and 2, 4, and 6 mm bone loss with first premolar extraction were constructed from a spiral CT scan of a skull. Archwire and brackets were modeled on the facial surfaces of teeth. Retraction force of 175 gm was applied from an orthodontic mini-implant placed bilaterally between the second premolar and first molar and 12 mm above plane of the archwire to anterior retraction hook (ARH) fixed at two heights of 6 and 10 mm above the archwire. RESULTS Maximum displacement and periodontal ligament (PDL) stress were calculated for different combinations of bone levels and ARH. As the bone loss increased, the tipping tendency, amount of intrusion, and maximum von Mises stress in PDL also increased, showing a direct correlation. CONCLUSION To minimize tipping and PDL stress, the height of ARH should be increased in alveolar bone loss conditions to allow retraction force to pass through or even above the center of resistance of anterior teeth. Even then, pure bodily retraction may not be achieved, but tipping tendency can be reduced. Nevertheless, it may not be suitable to increase ARH beyond a limit owing to chances of irritation to the vestibular mucosa. Alternative methods should be contemplated to reduce the tipping behavior. CLINICAL SIGNIFICANCE The alternative is to apply a lighter retraction force to reduce lingual tipping. A higher counter-moment in the archwire or bracket can also be incorporated.

Lowe syndrome and Dent II disease are X-linked monogenetic diseases characterised by a renal reabsorption defect in the proximal tubules and caused by mutations in the OCRL gene, which codes for an inositol-5-phosphatase. The life expectancy of patients suffering from Lowe syndrome is largely reduced because of the development of chronic kidney disease and related complications. There is a need for physiological human in vitro models for Lowe syndrome/Dent II disease to study the underpinning disease mechanisms and to identify and characterise potential drugs and drug targets. Here, we describe a proximal tubule organ on chip model combining a 3D tubule architecture with fluid flow shear stress that phenocopies hallmarks of Lowe syndrome/Dent II disease. We demonstrate the high suitability of our in vitro model for drug target validation. Furthermore, using this model, we demonstrate that proximal tubule cells lacking OCRL expression upregulate markers typical for epithelial–mesenchymal transition (EMT), including the transcription factor SNAI2/Slug, and show increased collagen expression and deposition, which potentially contributes to interstitial fibrosis and disease progression as observed in Lowe syndrome and Dent II disease.

Fas plays a major role in regulating ligand-induced apoptosis in many cell types. It is well known that several cancers demonstrate reduced cell surface levels of Fas and thus escape a potential control system via ligand-induced apoptosis, although underlying mechanisms are unclear. Here we report that the endosome associated trafficking regulator 1 (ENTR1), controls cell surface levels of Fas and Fas-mediated apoptotic signalling. ENTR1 regulates, via binding to the coiled coil domain protein Dysbindin, the delivery of Fas from endosomes to lysosomes thereby controlling termination of Fas signal transduction. We demonstrate that ENTR1 is cleaved during Fas-induced apoptosis in a caspase-dependent manner revealing an unexpected interplay of apoptotic signalling and regulation of endolysosomal trafficking resulting in a positive feedback signalling-loop. Our data provide insights into the molecular mechanism of Fas post-endocytic trafficking and signalling, opening possible explanations on how cancer cells regulate cell surface levels of death receptors., Fas is a death receptor that regulates apoptosis in many cell types and is downregulated on the cell surface in many cancers. Here, Sharma et al. show that endosome associated trafficking regulator ENTR1 regulates delivery of Fas to lysosomes, thereby controlling its degradation and signalling.