CNRS Pathology, Imaging and Orofacial Therapies

Paris, France

CNRS Pathology, Imaging and Orofacial Therapies

Paris, France

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Bartlett D.W.,King's College London | Lussi A.,University of Bern | West N.X.,Periodontology | Bouchard P.,CNRS Pathology, Imaging and Orofacial Therapies | And 2 more authors.
Journal of Dentistry | Year: 2013

To assess the prevalence of tooth wear on buccal/facial and lingual/palatal tooth surfaces and identify related risk factors in a sample of young European adults, aged 18-35 years. Calibrated and trained examiners measured tooth wear, using the basic erosive wear examination (BEWE) on in 3187 patients in seven European countries and assessed the impact of risk factors with a previously validated questionnaire. Each individual was characterized by the highest BEWE score recorded for any scoreable surface. Bivariate analyses examined the proportion of participants who scored 2 or 3 in relation to a range of demographic, dietary and oral care variables. The highest tooth wear BEWE score was 0 for 1368 patients (42.9%), 1 for 883 (27.7%), 2 for 831 (26.1%) and 3 for 105 (3.3%). There were large differences between different countries with the highest levels of tooth wear observed in the UK. Important risk factors for tooth wear included heartburn or acid reflux, repeated vomiting, residence in rural areas, electric tooth brushing and snoring. We found no evidence that waiting after breakfast before tooth brushing has any effect on the degree of tooth wear (p = 0.088). Fresh fruit and juice intake was positively associated with tooth wear. In this adult sample 29% had signs of tooth wear making it a common presenting feature in European adults. © 2013 Elsevier Ltd. All rights reserved.


Auger J.,pitaux Universitaires Paris Center | Le Denmat D.,CNRS Pathology, Imaging and Orofacial Therapies | Berges R.,French National Institute for Agricultural Research | Doridot L.,University of Paris Descartes | And 4 more authors.
Proceedings of the Royal Society B: Biological Sciences | Year: 2013

Digit length ratios, especially the second-to-fourth digit ratio (2D: 4D), are associated with various pathological and behavioural conditions in many species including humans and are dependent upon prenatal androgen to oestrogen balance. It is unknown whether digit ratios are modified by environmental exposure to ubiquitous endocrine disruptors. We studied the effect on adult maleWistar rat digit ratios of a gestational exposure to the oestrogenic and antiandrogenic compounds bisphenol A (BPA), genistein and vinclozolin, in low doses, and in combination with investigating in parallel a possible sexual dimorphism of this trait. We also investigated the effects on the male progeny not exposed during gestation. X-rays were taken of the left and right forepaws, and 2D-5D proximal to distal phalanx distances were measured by a standardized procedure based on semi-automatic image analysis. We provide evidence that there is a sexual dimorphism of digit ratios in the Wistar rat, and we found that BPA alone or in combination with genistein and vinclozolin significantly feminized digit ratios in male rats. Intriguingly, significant feminization of digit ratios was also found in the unexposed male progeny of males that had been exposed to compound mixtures. In conclusion, prenatal environmental levels of endocrine-active substances permanently disrupt digit ratios. Digit ratio measurement in adults is thus a promising biomarker of prenatal exposure to low-dose endocrine disruptors in rodents, with potential implications for future studies in humans. © 2013 The Author(s) Published by the Royal Society. All rights reserved.


Laiguillon M.-C.,French Institute of Health and Medical Research | Houard X.,French Institute of Health and Medical Research | Bougault C.,French Institute of Health and Medical Research | Gosset M.,CNRS Pathology, Imaging and Orofacial Therapies | And 8 more authors.
Arthritis Research and Therapy | Year: 2014

Introduction: Visfatin is an adipokine that may be involved in intertissular joint communication in osteoarthritis (OA). With a homodimeric conformation, it exerts nicotinamide phosphoribosyltransferase (Nampt) enzymatic activity, essential for nicotinamide adenine dinucleotide biosynthesis. We examined the tissular origin and conformation of visfatin/Nampt in human OA joints and investigated the role of visfatin/Nampt in chondrocytes and osteoblasts by studying Nampt enzymatic activity.Methods: Synovium, cartilage and subchondral bone from human OA joints were used for protein extraction or incubated for 24 hours in serum-free media (conditioned media), and synovial fluid was obtained from OA patients. Visfatin/Nampt expression in tissular extracts and conditioned media was evaluated by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Nampt activity was assessed in OA synovium by colorimetric assay. Primary cultures of murine chondrocytes and osteoblasts were stimulated with visfatin/Nampt and pretreated or not with APO866, a pharmacologic inhibitor of Nampt activity. The effect on cytokines, chemokines, growth factors and hypertrophic markers expression was examined by quantitative reverse transcriptase polymerase chain reaction and/or ELISA.Results: In tissular explants, conditioned media and synovial fluid, visfatin/Nampt was found as a homodimer, corresponding to the enzymatically active conformation. All human OA joint tissues released visfatin/Nampt (synovium: 628 ± 106 ng/g tissue; subchondral bone: 195 ± 26 ng/g tissue; cartilage: 152 ± 46 ng/g tissue), with significantly higher level for synovium (P <0.0005). Nampt activity was identified ex vivo in synovium. In vitro, visfatin/Nampt significantly induced the expression of interleukin 6, keratinocyte chemoattractant and monocyte chemoattractant protein 1 in chondrocytes and osteoblasts. APO866 decreased the mRNA and protein levels of these pro-inflammatory cytokines in the two cell types (up to 94% and 63% inhibition, respectively). Levels of growth factors (vascular endothelial growth factor, transforming growth factor β) and hypertrophic genes were unchanged with treatment.Conclusion: Visfatin/Nampt is released by all human OA tissues in a dimeric enzymatically active conformation and mostly by the synovium, which displays Nampt activity. The Nampt activity of visfatin is involved in chondrocyte and osteoblast activation, so targeting this enzymatic activity to disrupt joint tissue interactions may be novel in OA therapy. © 2014 Laiguillon et al.; licensee BioMed Central Ltd.


West N.X.,University of Bristol | Sanz M.,Complutense University of Madrid | Lussi A.,University of Bern | Bartlett D.,King's College London | And 2 more authors.
Journal of Dentistry | Year: 2013

Objectives Dentine hypersensitivity (DH) manifests as a transient but arresting oral pain. The incidence is thought to be rising, particularly in young adults, due to increases in consumption of healthy, yet erosive, diets. This study aimed to assess the prevalence of DH and relative importance of risk factors, in 18-35 year old Europeans. Methods In 2011, 3187 adults were enrolled from general dental practices in France, Spain, Italy, United Kingdom, Finland, Latvia and Estonia. DH was clinically evaluated by cold air tooth stimulation, patient pain rating (yes/no), accompanied by investigator pain rating (Schiff 0-3). Erosive toothwear (BEWE index 0-3) and gingival recession (mm) were recorded. Patients completed a questionnaire regarding the nature of their DH, erosive dietary intake and toothbrushing habits. Results 41.9% of patients reported pain on tooth stimulation and 56.8% scored ≥1 on Schiff scale for at least one tooth. Clinical elicited sensitivity was closely related to Schiff score and to a lesser degree, questionnaire reported sensitivity (26.8%), possibly reflecting the transient nature of the pain, alongside good coping mechanisms. Significant associations were found between clinically elicited DH and erosive toothwear and gingival recession. The questionnaire showed marked associations between DH and risk factors including heartburn/acid reflux, vomiting, sleeping medications, energy drinks, smoking and acid dietary intake. Conclusion Overall, the prevalence of DH was high compared to many published findings, with a strong, progressive relationship between DH and erosive toothwear, which is important to recognise for patient preventive therapies and clinical management of DH pain. © 2013 Elsevier Ltd.


Chaussain C.,CNRS Pathology, Imaging and Orofacial Therapies | Boukpessi T.,CNRS Pathology, Imaging and Orofacial Therapies | Khaddam M.,CNRS Pathology, Imaging and Orofacial Therapies | Tjaderhane L.,University of Turku | And 3 more authors.
Frontiers in Physiology | Year: 2013

Bacterial enzymes have long been considered solely accountable for the degradation of the dentin matrix during the carious process. However, the emerging literature suggests that host-derived enzymes, and in particular the matrix metalloproteinases (MMPs) contained in dentin and saliva can play a major role in this process by their ability to degrade the dentin matrix from within. These findings are important since they open new therapeutic options for caries prevention and treatment. The possibility of using MMP inhibitors to interfere with dentin caries progression is discussed. Furthermore, the potential release of bioactive peptides by the enzymatic cleavage of dentin matrix proteins by MMPs during the carious process is discussed. These peptides, once identified, may constitute promising therapeutical tools for tooth and bone regeneration. © 2013 Chaussain, Boukpessi, Khaddam, Tjaderhane, George and Menashi.


Bonnet N.,University of Geneva | Lesclous P.,CNRS Pathology, Imaging and Orofacial Therapies | Lesclous P.,University of Nantes | Saffar J.L.,CNRS Pathology, Imaging and Orofacial Therapies | Ferrari S.,University of Geneva
PLoS ONE | Year: 2013

Osteoporosis and periodontal disease (PD) are frequently associated in the elderly, both concurring to the loss of jaw alveolar bone and finally of teeth. Bisphosphonates improve alveolar bone loss but have also been associated with osteonecrosis of the jaw (ONJ), particularly using oncological doses of zoledronate. The effects and therapeutic margin of zoledronate on jaw bone therefore remain uncertain. We reappraised the efficacy and safety of Zoledronate (Zol) in ovariectomized (OVX) periostin (Postn)-deficient mice, a unique genetic model of systemic and jaw osteopenia. Compared to vehicle, Zol 1M (100 μg/kg/month) and Zol 1W (100 μg/kg/week) for 3 months both significantly improved femur BMD, trabecular bone volume on tissue volume (BV/TV) and cortical bone volume in both OVX Postn+/+ and Postn-/- (all p<0.01). Zol 1M and Zol 1W also improved jaw alveolar and basal BV/TV, although the highest dose (Zol 1W) was less efficient, particularly in Postn-/-. Zol decreased osteoclast number and bone formation indices, i.e. MAR, MPm/BPm and BFR, independently in Postn-/- and Postn+/+, both in the long bones and in deep jaw alveolar bone, without differences between Zol doses. Zol 1M and Zol 1W did not reactivate inflammation nor increase fibrous tissue in the bone marrow of the jaw, whereas the distance between the root and the enamel of the incisor (DRI) remained high in Postn-/- vs Postn+/+ confirming latent inflammation and lack of crestal alveolar bone. Zol 1W and Zol 1M decreased osteocyte numbers in Postn-/- and Postn+/+ mandible, and Zol 1W increased the number of empty lacunae in Postn-/-, however no areas of necrotic bone were observed. These results demonstrate that zoledronate improves jaw osteopenia and suggest that in Postn-/- mice, zoledronate is not sufficient to induce bone necrosis. © 2013 Bonnet et al.


Godlewski A.E.,Clermont University | Veyrune J.L.,Clermont University | Nicolas E.,Clermont University | CianguraCe C.A.,Hopital Pitie Salpetriere | And 6 more authors.
PLoS ONE | Year: 2011

Background: Patients scheduled for bariatric surgery (BS) are encouraged to chew slowly in order to optimise the digestion process. The influence of dental status on patients' ability to comply with advice on chewing behaviour is poorly documented. This study aims to compare modifications of chewing function before and after BS in three groups of obese patients differing in dental status. Method and Findings: A cohort of 46 obese women provided three groups: FD group: fully dentate (7-10 functional dental units [FU]); PD group: partially dentate (4-6 FU) without partial dentures; DW group: partial and complete denture wearers. Chewing time (CT), number of chewing cycles (CC), and chewing frequency (CF) were measured before and after surgery during mastication of standardised samples of raw carrot, peanuts, banana, apple and jelly. The median particle-size distribution (D50) of the pre-swallowed bolus was also evaluated for peanut and carrot. Before surgery, the PD and DW groups exhibited greater mean CCs and CTs than the FD group (SNK p<0.05) and produced a bolus with higher granulometry (SNK, p<0.05) than the FD group. After surgery, CT and CC increased for all groups and for all foods, but not statistically significant for jelly. The resulting changes in bolus granulometry observed depended on both food and dental status. The granulometry of carrot bolus remained as fine or as coarse in FD and DW groups respectively as it was before surgery while it was significantly decreased in the PD group (Student's test, p<0.001). Conclusions: After bariatric surgery, all the obese patients, regardless of dental status modified their chewing kinematics. The effects of this chewing behaviour on bolus granulometry depended on dental status and type of food. Further studies are needed to understand better the impact of dental status on feeding behaviour and nutrition in patients with obesity. © 2011 Godlewski et al.


PubMed | French National Center for Scientific Research, CNRS Pathology, Imaging and Orofacial Therapies, University of Paris Descartes and University Paris Diderot
Type: Journal Article | Journal: Stem cells translational medicine | Year: 2016

Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF.


Boukpessi T.,CNRS Pathology, Imaging and Orofacial Therapies | Gaucher C.,CNRS Pathology, Imaging and Orofacial Therapies | Gaucher C.,French Institute of Health and Medical Research | Leger T.,University Paris Diderot | And 7 more authors.
American Journal of Pathology | Year: 2010

Severe dental troubles are associated with X-linked hypophosphatemic rickets and are mainly related to impaired dentin mineralization. In dentin matrix, matrix extracellular phosphoglycoprotein (MEPE) may be protected from proteolysis by a specific interaction with PHEX (phosphate regulating gene with homologies to endopeptidases on the X chromosome). The objective of our work was to determine whether PHEX impairment induces MEPE cleavage in dentin and the subsequent release of the C-terminal acidic serine- and aspartate-rich motif (ASARM) peptide, which is known to inhibit mineralization. By Western blot analysis, we explored dentin extracts from seven hypophosphatemic patients with mutations of the PHEX gene. A proteomic approach combining immunoprecipitation, surface-enhanced laser desorption/ionization-time of flight-mass spectrometry and matrix-assisted laser desorption ionizationtime of flight analysis of the samples completed this exploration. This study shows a 4.1-kDa peptide containing the MEPE-derived ASARM peptide in hypophosphatemic samples. The presence of ASARM was less marked in patients treated with 1-hydroxylated vitamin D and phosphate during growth. Moreover, recombinant ASARM implanted in a rat pulp injury model disturbed the formation of the reparative dentin bridge. These results suggest that abnormal MEPE cleavage occurs when PHEX activity is deficient in humans, the ASARM peptide may be involved in the mineralization defects and the PHEXMEPE interaction may be indirect, as ensuring a better phosphate and vitamin D environment to the mineralizing dentin prevents MEPE cleavage. Copyright © American Society for Investigative Pathology.


Rochefort G.Y.,CNRS Pathology, Imaging and Orofacial Therapies
Therapeutic Advances in Musculoskeletal Disease | Year: 2014

Osteoporosis is characterized by a low bone-mineral density associated with skeletal fractures. The decrease in bone-mineral density is the consequence of an unbalanced bone-remodeling process, with higher bone resorption than bone formation. The orchestration of the bone-remodeling process is under the control of the most abundant cell in bone, the osteocyte. Functioning as an endocrine cell, osteocytes are also a source of soluble factors that not only target cells on the bone surface, but also target distant organs. Therefore, any drugs targeting the osteocyte functions and signaling pathways will have a major impact on the bone-remodeling process. This review discusses potential advances in drug therapy for osteoporosis, including novel osteocyte-related antiresorptive and anabolic agents that may become available in the coming years. © The Author(s), 2014.

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