From Vascular Smooth Muscle Cells to Folliculogenesis: What About Vasorin?

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

Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis

Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ) permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL). Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), were recently shown to be also involved in Amelogenesis Imperfecta (AI). In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO) mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis

How much energy do we need to ablate 1 mm3 of stone during Ho:YAG laser lithotripsy? An in vitro study

Introduction: Holmium:yttrium–aluminium–garnet (Ho:YAG) is currently the gold standard for lithotripsy for the treatment of all known urinary stone types. Stone composition and volume are major determinants of the lithotripsy. This in vitro study evaluated the required energy to ablate 1 mm3 of various stone types with different laser settings using Ho:YAG. Methods: 272 µm core-diameter laser fibers (Boston Scientific©) were connected to a 30 Watt MH1 Ho:YAG generator (Rocamed®). An experimental setup consisting of immerged human stones of calcium oxalate monohydrate (COM), uric acid (UA) or cystine (Cys) was used with a single pulse lasing emission (0.6/0.8/1 J), in contact mode. Stones were dried out before three-dimensional scanning to measure ablation volume per pulse (AVP) and required energy to treat 1 mm3 (RE). Results: All settings considered, ablation volumes per pulse (AVP) for COM were significantly lower than those for UA and Cys (p = 0.002 and p = 0.03, respectively), whereas AVP for Cys was significantly lower than those for UA (p = 0.03). The mean REs at 0.6 J pulse energy (PE) for COM, Cys and UA were 34, 8.5 and 3.2 J, respectively The mean REs at 1 J PE for COM, Cys and UA were 14.7, 6.4 and 2 J, respectively. At 0.6 J PE, RE for COM was more than tenfold and fivefold higher than those for UA and Cys, respectively. Conclusion: This in vitro study shows for the first time a volumetric evaluation of Ho:YAG efficiency by the ablation volume per pulse on human stone samples, according to various pulse energies. The REs for COM, UA and Cys should be considered in clinical practice.In vivo imaging was performed at Life Imag-ing Facility of Paris Descartes University (Plateforme Imageries du Vivant), supported by France Life Imaging (grant ANR-11-INBS-0006) and Infrastructures Biologies-Santé

Rôle de protéines non collagéniques dans la physiopathologie de la dentine humaine

Ce travail a pour objectif principal d'étudier la physiopathologie de la matrice dentinaire. Dans ce but, deux modèles de pathologie de la dentine ont servi de support: la carie dentinaire et la dentine hypophosphatémique. A travers ces modèles, nous avons cherché à mieux comprendre le rôle des protéines non collagéniques dans la minéralisation, la structure et la dégradation de la dentine humaine. Dans le premier modèle, le rôle des MMPs dentinaires dans la dégradation des protéines de la dentine cariée a été tout particulièrement développé. Ainsi, nous avons essayé de comprendre comment la MMP-3 (dont la présence dans la dentine humaine mature a été démontrée pour la première fois par ce travail) initiait la libération des molécules de la matrice extracellulaire dentinaire à partir de dentine humaine artificiellement déminéralisée. Ce premier travail ouvre des perspectives d'une part en ternie de réparation de la dent, la dégradation de matrice pouvant fournir des peptides bioactifs, et d'autre part et à plus court terme, en terme de thérapeutique adhésive. En effet, un traitement de la dentine par des MMPs pourrait améliorer le collage d'un composite à la dentine traitée. Le deuxième modèle concerne la dentine de dents de patients atteints de rachitisme hypophosphatémique lié à la mutation de PHEX. Chez ces patients, des défauts de minéralisation de la dentine sont observés. Nous avons étudié la structure, la composition et la distribution des molécules de la matrice extracellulaire dentinaire de dents temporaires provenant de patients hypophosphatémiques. Nous avons ainsi montré une accumulation des protéines de la matrice sous forme dégradée au niveau des plages de dentine non minéralisée. Dans ces conditions pathologiques, MEPE semble jouer un rôle critique et notre travail a ^contribué àjme meilleure compréhension de ses fonctions.The aim of this work was to study the physiopathology of dentin extracellular matrix. With this end, two models of pathological dentin were carried out: artificial caries-affected dentin and hypophosphatemic dentin. Through these models, we tried to better understand the role of non collagenous proteins in the mineralization, the structure and the degradation of human dentin. Therefore, in the first model, we investigated how recombinant MMP-3 initiates the release of ECM molecules from artificially demineralized human dentin. That way, we identified for the first time to the best of our knowledge, the presence of endogenous MMP-3 in mature dentin. In this first approach, the use of MMP-3 as a potential agent for dentin preparation may improve resin adhesion. The second model concerned dentin from hypophosphatemic patients. Familial hypophosphatemic rickets results from the mutation of the PHEX gene. Patients have reported to display important dentin defects, and therefore, we explored the dentin structure, composition, and distribution of ECM molecules in hypophosphatemic human deciduous teeth. The abnormal presence of low-molecular weight protein complexes in large interglobular spaces was shown. In these pathological conditions, MEPE seems to display important role and our work aimed to better understand this function.MONTROUGE-BUFR Odontol.PARIS5 (920492101) / SudocSudocFranceF

Rôle du fibroblaste dermique et gingival dans la cicatrisation (Modulation de l'organisation matricielle in vitro)

MONTROUGE-BUFR Odontol.PARIS5 (920492101) / SudocSudocFranceF

Matrix Metalloproteinases and Other Matrix Proteinases in Relation to Cariology : The Era of 'Dentin Degradomics'

Dentin organic matrix, with type I collagen as the main component, is exposed after demineralization in dentinal caries, erosion or acidic conditioning during adhesive composite restorative treatment. This exposed matrix is prone to slow hydrolytic degradation by host collagenolytic enzymes, matrix metalloproteinases (MMPs) and cysteine cathepsins. Here we review the recent findings demonstrating that inhibition of salivary or dentin endogenous collagenolytic enzymes may provide preventive means against progression of caries or erosion, just as they have been shown to retain the integrity and improve the longevity of resin composite filling bonding to dentin. This paper also presents the case that the organic matrix in caries-affected dentin may not be preserved as intact as previously considered. In partially demineralized dentin, MMPs and cysteine cathepsins with the ability to cleave off the terminal non-helical ends of collagen molecules (telopeptides) may lead to the gradual loss of intramolecular gap areas. This would seriously compromise the matrix ability for intrafibrillar remineralization, which is considered essential in restoring the dentin's mechanical properties. More detailed data of the enzymes responsible and their detailed function in dentin-destructive conditions may not only help to find new and better preventive means, but better preservation of demineralized dentin collagenous matrix may also facilitate true biological remineralization for the better restoration of tooth structural and mechanical integrity and mechanical properties. (C) 2015 S. Karger AG, BaselPeer reviewe

Strategies Developed to Induce, Direct, and Potentiate Bone Healing

Bone exhibits a great ability for endogenous self-healing. Nevertheless, impaired bone regeneration and healing is on the rise due to population aging, increasing incidence of bone trauma and the clinical need for the development of alternative options to autologous bone grafts. Current strategies, including several biomolecules, cellular therapies, biomaterials, and different permutations of these, are now developed to facilitate the vascularization and the engraftment of the constructs, to recreate ultimately a bone tissue with the same properties and characteristics of the native bone. In this review, we browse the existing strategies that are currently developed, using biomolecules, cells and biomaterials, to induce, direct and potentiate bone healing after injury and further discuss the biological processes associated with this repair

Le rôle du chirurgien-dentiste dans la nutrition

MONTROUGE-BUFR Odontol.PARIS5 (920492101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Phosphorylated and Non-phosphorylated Leucine Rich Amelogenin Peptide Differentially Affect Ameloblast Mineralization

The Leucine Rich Amelogenin Peptide (LRAP) is a product of alternative splicing of the amelogenin gene. As full length amelogenin, LRAP has been shown, in precipitation experiments, to regulate hydroxyapatite (HAP) crystal formation depending on its phosphorylation status. However, very few studies have questioned the impact of its phosphorylation status on enamel mineralization in biological models. Therefore, we have analyzed the effect of phosphorylated (+P) or non-phosphorylated (−P) LRAP on enamel formation in ameloblast-like cell lines and ex vivo cultures of murine postnatal day 1 molar germs. To this end, the mineral formed was analyzed by micro-computed tomography, Field Emission Scanning Electron Microscopy, Transmission Electron Microscopy, Selected Area Electon Diffraction imaging. Amelogenin gene transcription was evaluated by qPCR analysis. Our data show that, in both cells and germ cultures, LRAP is able to induce an up-regulation of amelogenin transcription independently of its phosphorylation status. Mineral formation is promoted by LRAP(+P) in all models, while LRAP(–P) essentially affects HAP crystal formation through an increase in crystal length and organization in ameloblast-like cells. Altogether, these data suggest a differential effect of LRAP depending on its phosphorylation status and on the ameloblast stage at the time of treatment. Therefore, LRAP isoforms can be envisioned as potential candidates for treatment of enamel lesions or defects and their action should be further evaluated in pathological models

L' évaluation du risque carieux

MONTROUGE-BUFR Odontol.PARIS5 (920492101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF