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1. Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

Author

Domblides, Charlotte, Rochefort, Juliette, Riffard, Clémence, Panouillot, Marylou, Lescaille, Géraldine, Teillaud, Jean-Luc, Mateo, Véronique, Dieu-Nosjean, Marie-Caroline, Immunology from Concept and Experiments to Translation (ImmunoConcept), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Service d'Odontologie = Service de médecine Bucco-dentaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), and Gestionnaire, HAL Sorbonne Université 5

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, organoid, Immunology, therapeutic intervention, Review, artificial intelligence, tumor model, Tertiary Lymphoid Structures, Neoplasms, Tumor Microenvironment, [SDV.IMM]Life Sciences [q-bio]/Immunology, biomarker, cancer, Animals, Humans, tertiary lymphoid structure, lymphoid neogenesis
Abstract

International audience; The tumor microenvironment is a complex ecosystem almost unique to each patient. Most of available therapies target tumor cells according to their molecular characteristics, angiogenesis or immune cells involved in tumor immune-surveillance. Unfortunately, only a limited number of patients benefit in the long-term of these treatments that are often associated with relapses, in spite of the remarkable progress obtained with the advent of immune checkpoint inhibitors (ICP). The presence of “hot” tumors is a determining parameter for selecting therapies targeting the patient immunity, even though some of them still do not respond to treatment. In human studies, an in-depth analysis of the organization and interactions of tumor-infiltrating immune cells has revealed the presence of an ectopic lymphoid organization termed tertiary lymphoid structures (TLS) in a large number of tumors. Their marked similarity to secondary lymphoid organs has suggested that TLS are an “anti-tumor school” and an “antibody factory” to fight malignant cells. They are effectively associated with long-term survival in most solid tumors, and their presence has been recently shown to predict response to ICP inhibitors. This review discusses the relationship between TLS and the molecular characteristics of tumors and the presence of oncogenic viruses, as well as their role when targeted therapies are used. Also, we present some aspects of TLS biology in non-tumor inflammatory diseases and discuss the putative common characteristics that they share with tumor-associated TLS. A detailed overview of the different pre-clinical models available to investigate TLS function and neogenesis is also presented. Finally, new approaches aimed at a better understanding of the role and function of TLS such as the use of spheroids and organoids and of artificial intelligence algorithms, are also discussed. In conclusion, increasing our knowledge on TLS will undoubtedly improve prognostic prediction and treatment selection in cancer patients with key consequences for the next generation immunotherapy.

Published
2021
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2. The Potential of FGF-2 in Craniofacial Bone Tissue Engineering: A Review

Author

Catherine Chaussain, Anita Novais, Eirini Chatzopoulou, Caroline Gorin, Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Université de Paris – UFR Odontologie Garancière [Santé] (UP UFR Odontologie G), and Université de Paris (UP)

Subjects
0301 basic medicine, QH301-705.5, [SDV]Life Sciences [q-bio], medicine.medical_treatment, FGF-2, Review, Fibroblast growth factor, Bioinformatics, Models, Biological, Bone remodeling, 03 medical and health sciences, Therapeutic approach, angiogenesis, 0302 clinical medicine, Tissue engineering, Animals, Homeostasis, Humans, Medicine, mineralization, Biology (General), Craniofacial, bone tissue engineering, Craniofacial bone, Tissue Engineering, business.industry, Growth factor, Skull, Biomaterial, General Medicine, signaling pathways, 030104 developmental biology, Face, 030220 oncology & carcinogenesis, Fibroblast Growth Factor 2, business
Abstract

International audience; Bone is a hard-vascularized tissue, which renews itself continuously to adapt to the mechanical and metabolic demands of the body. The craniofacial area is prone to trauma and pathologies that often result in large bone damage, these leading to both aesthetic and functional complications for patients. The "gold standard" for treating these large defects is autologous bone grafting, which has some drawbacks including the requirement for a second surgical site with quantity of bone limitations, pain and other surgical complications. Indeed, tissue engineering combining a biomaterial with the appropriate cells and molecules of interest would allow a new therapeutic approach to treat large bone defects while avoiding complications associated with a second surgical site. This review first outlines the current knowledge of bone remodeling and the different signaling pathways involved seeking to improve our understanding of the roles of each to be able to stimulate or inhibit them. Secondly, it highlights the interesting characteristics of one growth factor in particular, FGF-2, and its role in bone homeostasis, before then analyzing its potential usefulness in craniofacial bone tissue engineering because of its proliferative, pro-angiogenic and pro-osteogenic effects depending on its spatial-temporal use, dose and mode of administration.

Published
2021
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3. Systemic Lupus Erythematosus and Periodontal Disease: A Complex Clinical and Biological Interplay

Author

Antoine Zalcberg, Fani Anagnostou, Bouchra Sojod, Cibele Pidorodeski Nagano, Sophie Myriam Dridi, Glenda Melissa Garcia Lopez, Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Biologie, Bioingénierie et Bioimagerie Ostéo-articulaires (B3OA (UMR_7052)), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Université Côte d'Azur (UCA)

Subjects
medicine.medical_specialty, periodontal disease, Translational research, Review, Systemic inflammation, 03 medical and health sciences, 0302 clinical medicine, Periodontal disease, Immunity, periopathogens, Epidemiology, medicine, risk factors, skin and connective tissue diseases, systematic lupus erythematosus, periodontitis, Organ system, 030203 arthritis & rheumatology, Periodontitis, Autoimmune disease, business.industry, 030206 dentistry, General Medicine, autoimmune and inflammatory diseases, medicine.disease, 3. Good health, Immunology, Medicine, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Reports on the association of periodontal disease (PD) with systemic lupus erythematosus (SLE) have regularly been published. PD is a set of chronic inflammatory conditions linked to a dysbiotic microbial biofilm, which affects the periodontal tissues, resulting eventually in their destruction and contributing to systemic inflammation. SLE is a multi-system chronic inflammatory autoimmune disease that has a wide range of clinical presentations, touching multiple organ systems. Many epidemiological studies have investigated the two-way relationship between PD and SLE, though their results are heterogeneous. SLE and PD are multifactorial conditions and many biological-based hypotheses suggest common physiopathological pathways between the two diseases, including genetics, microbiology, immunity, and environmental common risk factors. By focusing on recent clinical and translational research, this review aimed to discuss and give an overview of the relationship of SLE with PD, as well as looking at the similarities in the immune-pathological aspects and the possible mechanisms connecting the development and progression of both diseases.

Published
2021
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4. Clinical and numerical study of a statically determinate lingual mechanism for orthodontic tooth displacement

Author

Florent Goussard, R. Licha, G. Dot, V. Sansalone, Laboratoire Modélisation et Simulation Multi-Echelle (MSME), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche en Paléontologie - Paris (CR2P), Muséum national d'Histoire naturelle (MNHN)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Odontologie = Service de médecine Bucco-dentaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Orthodontics, Statically indeterminate, Computer science, [SDV]Life Sciences [q-bio], 0206 medical engineering, Biomedical Engineering, Biomechanics, Bioengineering, 030229 sport sciences, 02 engineering and technology, General Medicine, 020601 biomedical engineering, Computer Science Applications, Human-Computer Interaction, Mechanism (engineering), 03 medical and health sciences, 0302 clinical medicine, Tooth movement, Displacement (orthopedic surgery)
Abstract

International audience; Numerical simulation of long term orthodontic tooth movement could help clinicians to plan more efficient and mechanically sound treatments (Burstone 2015). It remains a challenge and no prospective model exists yet. Finite element analysis (FEA) has been used by several authors to perform such simulations, but these studies usually lack of experimental calibration or validation (Schneider et al. 2002; Kojima and Fukui 2012; Chen et al. 2014). Moreover, a proper definition of the boundary conditions of the model is a critical issue as most of the orthodontic forces are statically indeterminate (Hamanaka et al. 2017).Our main objective was to perform a numerical study of orthodontic tooth displacement based on precise clinical data. We collected monthly three-dimensional (3D) displacement data of two canines submitted to a known force system. Then, we calibrated a preliminary patient-specific FEA model from these acquisitions.

Published
2020
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5. Hedging against Neuropathic Pain: Role of Hedgehog Signaling in Pathological Nerve Healing

Author

Nathan, Moreau, Yves, Boucher, Hôpital Bretonneau, Université de Paris – UFR Odontologie Montrouge [Santé] (UP UFR Odontologie M), Université de Paris (UP), Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Paris – UFR Odontologie Garancière [Santé] (UP UFR Odontologie G), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
neuropathic pain, Wound Healing, [SDV]Life Sciences [q-bio], Disease Management, desert hedgehog, Review, Nerve Regeneration, lcsh:Chemistry, sonic hedgehog, lcsh:Biology (General), lcsh:QD1-999, Peripheral Nerve Injuries, Morphogenesis, Homeostasis, Humans, Neuralgia, Pain Management, peripheral nerve injury, nerve healing, Hedgehog Proteins, Disease Susceptibility, Peripheral Nerves, lcsh:QH301-705.5, Signal Transduction
Abstract

International audience; The peripheral nervous system has important regenerative capacities that regulate and restore peripheral nerve homeostasis. Following peripheral nerve injury, the nerve undergoes a highly regulated degeneration and regeneration process called Wallerian degeneration, where numerous cell populations interact to allow proper nerve healing. Recent studies have evidenced the prominent role of morphogenetic Hedgehog signaling pathway and its main effectors, Sonic Hedgehog (SHH) and Desert Hedgehog (DHH) in the regenerative drive following nerve injury. Furthermore, dysfunctional regeneration and/or dysfunctional Hedgehog signaling participate in the development of chronic neuropathic pain that sometimes accompanies nerve healing in the clinical context. Understanding the implications of this key signaling pathway could provide exciting new perspectives for future research on peripheral nerve healing.

Published
2020
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6. Osteoformation potential of an allogenic partially demineralized bone matrix in critical-size defects in the rat calvarium

Author

Henri Michel Benoist, Ahmad Moustapha Diallo, Michel Boissière, Raphael Bardonnet, Morad Bensidhoum, Emmanuel Pauthe, Hervé Petite, Fani Anagnostou, Solène Rota, CY Cergy Paris Université (CY), Equipe de recherche sur les relations matrice extracellulaire-cellules (ERRMECe), Fédération INSTITUT DES MATÉRIAUX DE CERGY-PONTOISE (I-MAT), CY Cergy Paris Université (CY)-CY Cergy Paris Université (CY), Biologie, Bioingénierie et Bioimagerie Ostéo-articulaires (B3OA (UMR_7052)), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Materials science, Bone Regeneration, Bone Matrix, Bioengineering, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biomaterials, Hydroxyproline, chemistry.chemical_compound, In vivo, Osteogenesis, Animals, Fourier transform infrared spectroscopy, Bone regeneration, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Bone allograft, Bone Transplantation, Demineralized bone matrix, Skull, 021001 nanoscience & nanotechnology, Autologous bone, 0104 chemical sciences, Rats, Demineralization, chemistry, Mechanics of Materials, 0210 nano-technology, Biomedical engineering
Abstract

International audience; Allogenic demineralized bone matrix has been developed as a reliable alternative to the autologous bone graft. In the present study, we assessed the osteoformation potential of a partially demineralized bone matrix (PDBM) in a paste form obtained without an added carrier. This formulation included the preparation of cancelous bone from femoral heads after decellularision, delipidation, demineralization in HCl and autoclaving at 121 • C. Structural and biochemical characteristics of PDBM were determined using FTIR (Fourier transform infrared spectroscopy), hydroxyproline, DNA content assays, and optical ellipsometry. The osteoformation potential was evaluated in 8-, 6-, and 4-mm-diameter rat-calvarial bone defects by in vivo micro-CT analysis, performed immediately after surgery on days 0, 15, 30, 45, and 60. Moreover, histological and histomorphometric analyses were done on day 60. PDBM was compared to cancelous bone powder (BP) before its partial demineralization. The expression levels of selected inflammation-, angiogenesis-, and bone-related genes were also investigated by RT-PCR, 3, 7, and 14 days after surgery. Compared to the control group, the PDBM group exhibited a significant increase (p < 0.05) in radiopacity in 8-mm-and 6-mm-diameter defects at all time points tested. On day 60, the amount of newly-formed bone was greater (16 and 1.6 folds; p < 0.001; respectively) compared to that in control defects. No bone formation was observed in defects filled with BP regardeless of the size. In 8-mm-diameter defect, PDBM was effective enough to induce the upregulation of genes pertinent to inflammation (i.e., TNFα, IL-6, and IL-8), angiogenesis (i.e., VEGF, VWF), and osteogenesis (ALP, RUNX2, BGLAP, SP7) by day 3 after surgery. This study showed that the tested PDBM deeply influences the early critical events involved in bone regeneration and exhibits efficient osteoformation capacity, making it an attractive graft option for treating defects in periodontal and maxillofacial areas.

Published
2020
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7. Primary Retention of Molars and RANKL Signaling Alteration during Craniofacial Growth 3

Author

Gama, Andrea, Maman, Laura, William Vargas-Franco, Jorge, Omar, Rana, Brounais-Le Royer, Benedicte, Yagita, Hideo, Babajko, Sylvie, Berdal, Ariane, Acevedo, Ana, Heymann, Dominique, Lezot, Frederic, Castaneda, Beatriz, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Odontology Center of District Federal Military Police [Brasília, Brazil], University of Brasilia [Brazil] (UnB), Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), University of Antioquia [Medellin, AA, Colombia], Juntendo University School of Medicine [Tokyo, Japan], Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire de Biologie des Cancers et de Théranostic [St Herblain, Nantes] (LabCT), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Department of Oncology and Metabolism [Sheffield, UK] (INSERM European Associated Laboratory 'Sarcoma Research Unit'), The University of Sheffield [Sheffield, U.K.], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Service d'Odontologie = Service de médecine Bucco-dentaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Heymann, Dominique

Subjects
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, growth, RANKL, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, craniofacial, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, stomatognathic system, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], primary retention of molars
Abstract

International audience; The primary retention of molars observed in clinic corresponds to a still-unexplained 29 absence of molar eruption despite the presence of an eruption pathway, resembling the 30 experimental transient inhibition of RANKL signaling in mice. The aim of the present study was to 31 confront the hypothesis according to which the primary retention of molars is associated with 32 transitory perturbations to RANKL signaling during growth as part of a wider craniofacial skeleton 33 pattern. The experimental strategy was based on combining a clinical study and an animal study 34 corresponding to characterization of the craniofacial phenotypes of patients with primary retention 35 of molars and analyses in mice of the consequences of transient inhibition of RANKL signaling on 36 molar eruption and craniofacial growth. The clinical study validated the existence of a particular 37 craniofacial phenotype in patients with primary retention of molars: a retromandibular skeletal 38 class II typology with reduced mandibular dimensions, which manifests itself at the dental level by 39 a class II/2 with palatoversion of the upper incisors and anterior overbite. The animal study 40 demonstrated that transient invalidation of RANKL signaling had an impact on the molar eruption 41 process, the severity of which was dependent on the period of inhibition, and was associated with a 42 reduction in two craniofacial morphometric parameters: total skull length and craniofacial vault 43 length. In conclusion, primary retention of molars may be proposed as part of the craniofacial 44 skeleton phenotype associated with a transitory alteration in RANKL signaling during growth. 45

Published
2020
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8. Origins of Alterations to Rankl Null Mutant Mouse Dental Root Development

Author

Jorge William Vargas-Franco, Dominique Heymann, Jérôme Amiaud, Diana Carolina Sánchez Mesa, Sylvie Babajko, Ana Carolina Acevedo, Andrea Gama, Frédéric Lézot, Elizabeth Restrepo Bedoya, Ariane Berdal, Beatriz Castaneda, Heymann, Dominique, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Department of Basic Studies [Medellin, AA, Colombia], University of Antioquia [Medellin, AA, Colombia], Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Brasilia [Brazil] (UnB), Department of Oncology and Metabolism [Sheffield, UK], The University of Sheffield [Sheffield, U.K.], Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service d'Odontologie = Service de médecine Bucco-dentaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
musculoskeletal diseases, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], RANKL/RANK signaling, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, root formation, Biology, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Catalysis, Bone resorption, lcsh:Chemistry, Inorganic Chemistry, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, Bone cell, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Physical and Theoretical Chemistry, tooth, lcsh:QH301-705.5, Molecular Biology, Spectroscopy, Dental alveolus, 030304 developmental biology, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Organic Chemistry, Hertwig's epithelial root sheath, Hertwig’s epithelial root sheath, General Medicine, Periodontium, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Computer Science Applications, Cell biology, Proliferating cell nuclear antigen, lcsh:Biology (General), lcsh:QD1-999, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, RANKL, 030220 oncology & carcinogenesis, biology.protein, Immunohistochemistry, bone resorption
Abstract

The purpose of the present study was to assess the early stages of development of mouse first molar roots in the osteopetrotic context of RANKL invalidation in order to demonstrate that the radicular phenotype observed resulted not only from defective osteoclasts, but also from loss of cell-to-cell communication among dental, periodontium and alveolar bone cells involving RANKL signaling. Two experimental models were used in this study: Rankl mutants with permanent RANKL invalidation, and C57BL/6J mice injected during the first postnatal week with a RANKL neutralizing antibody corresponding to a transient RANKL invalidation. The dento-alveolar complex was systematically analyzed using micro-CT, and histological and immunohistochemical approaches. These experiments showed that the root elongation alterations observed in the Rankl-/- mice were associated with reduced proliferation of the RANK-expressing HERS cells with a significant decrease in proliferating cell nuclear antigen (PCNA) expression and a significant increase in P21 expression. The phenotypic comparison of the adult first molar root at 35 days between permanent and transitory invalidations of RANKL made it possible to demonstrate that alterations in dental root development have at least two origins, one intrinsic and linked to proliferation/differentiation perturbations in dental-root-forming cells, the other extrinsic and corresponding to disturbances of bone cell differentiation/function.

Published
2020
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9. Are changes in the stomatognatic system able to modify the eye balance in dyslexia?

Author

Anne-Marie Bouvier, Yves Boucher, Valérie Jooste, Alexandre Mettey, Patrick Quercia, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Odontologie = Service de médecine Bucco-dentaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CCSD, Accord Elsevier

Subjects
medicine.medical_specialty, Visual perception, genetic structures, Sensory system, Audiology, Vertical heterophoria, Article, Dental occlusion, Postural control, Correlation, Dyslexia, 03 medical and health sciences, 0302 clinical medicine, medicine, Eye balance, General Dentistry, Balance (ability), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, 030206 dentistry, medicine.disease, Otorhinolaryngology, 030220 oncology & carcinogenesis, Oral sensory innervation, sense organs, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Objectives To clarify the link between eye muscle function and oral information by comparing 21 dyslexic readers (DR) and 14 normal readers (NR). Methods Changes in vertical heterophoria (VH) were measured using the Maddox Rod Test performed according to oral modifications and postural conditions. The Spearman correlation was used to assess whether reading delay was correlated with the lability index. Results Overall, 50% of NR children and 81% of DR experienced at least one variation in visual perception (p = 0.053). Among DR, the less reading delay they had, the higher their index of lability (p = 0.026), whereas there was no significant correlation among NR. Changes in the Maddox Test were more frequent in DR than in NR after the addition of sensory and postural stimuli, except for one specific posture. For sensory stimuli, the mean lability index was 1.35 in NR and 4.19 in DR, (p = 0.001). For postural stimuli, it was 0.71 and 2.61, (p = 0.003). Conclusions It is possible to modify visual perception by changing sensory or mechanical stimuli. Changes are more frequent in DR than in NR. Postural control can be improved with guided oral stimulations. Significance These results reinforce the importance of professional cooperation in the care of dyslexic readers.

Published
2019
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10. Type 2 diabetes alters mesenchymal stem cell secretome composition and angiogenic properties

Author

Guavri Caliaperoumal, Jonathan Ribot, Fani Anagnostou, Catherine Boisson-Vidal, Joseph Paquet, Hervé Petite, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Bioingénierie et Bioimagerie Ostéo-articulaires, Biomécanique et Biomatériaux Ostéo-Articulaires (B2OA (UMR_7052)), École nationale vétérinaire - Alfort (ENVA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Innovations thérapeutiques en hémostase (IThEM - U1140), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA), Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Biomécanique et Biomatériaux Ostéo-Articulaires ( B2OA ), Université Paris Diderot - Paris 7 ( UPD7 ) -Ecole Nationale Vétérinaire d'Alfort-Centre National de la Recherche Scientifique ( CNRS ), Innovations thérapeutiques en hémostase ( IThEM - U1140 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL UPMC, Gestionnaire, Service d'Odontologie = Service de médecine Bucco-dentaire [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Proteomics, 0301 basic medicine, Proteome, endocrine system diseases, Angiogenesis, MSCs, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Type 2 diabetes, Extracellular matrix, angiogenesis, 0302 clinical medicine, Cell Movement, Insulin-Like Growth Factor I, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Extracellular Matrix Proteins, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, endothelial cells, Endothelial stem cell, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Molecular Medicine, Original Article, medicine.medical_specialty, Cell Survival, Mice, Nude, Neovascularization, Physiologic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Diabetes Mellitus, Experimental, 03 medical and health sciences, In vivo, Internal medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Human Umbilical Vein Endothelial Cells, medicine, Animals, Cell Proliferation, diabetes type 2, Gene Expression Profiling, Mesenchymal stem cell, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], nutritional and metabolic diseases, Mesenchymal Stem Cells, Original Articles, Cell Biology, medicine.disease, In vitro, Rats, Zucker, secretome, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Culture Media, Conditioned, Bone marrow, Reactive Oxygen Species
Abstract

International audience; This study aimed at characterizing the impact of type 2 diabetes mellitus (T2DM) on the bone marrow mesenchymal stem cell (BMMSC) secre-tome and angiogenic properties. BMMSCs from Zucker diabetic fatty rats (ZDF) (a T2DM model) and Zucker LEAN littermates (control) were cultured. The supernatant conditioned media (CM) from BMMSCs of diabetic and control rats were collected and analysed. Compared to results obtained using CM from LEAN-BMMSCs, the bioactive content of ZDF-BMMSC CM (i) differently affects endothelial cell (HUVEC) functions in vitro by inducing increased (3.5-fold; P < 0.01) formation of tubule-like structures and migration of these cells (3-fold; P < 0.001), as well as promotes improved vascular formation in vivo, and (ii) contains different levels of angiogenic factors (e.g. IGF1) and mediators, such as OSTP, CATD, FMOD LTBP1 and LTBP2, which are involved in angiogenesis and/or extracellular matrix composition. Addition of neutralizing antibodies against IGF-1, LTBP1 or LTBP2 in the CM of BMMSCs from diabetic rats decreased its stimulatory effect on HUVEC migration by approximately 60%, 40% or 40%, respectively. These results demonstrate that BMMSCs from T2DM rats have a unique secretome with distinct angiogenic properties and provide new insights into the role of BMMSCs in aberrant angiogenesis in the diabetic milieu.

Published
2016
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11. Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Author

Rebecca Landon, Fani Anagnostou, Hervé Petite, Cyprien Denoeud, Jonathan Ribot, Morad Bensidhoum, Graciela Pavon-Djavid, Guilhem Frescaline, Biologie, Bioingénierie et Bioimagerie Ostéo-articulaires (B3OA (UMR_7052)), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, HAL Sorbonne Université 5, Biologie, Bioingénierie et Bioimagerie Ostéo-articulaires (B3OA), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service d'Odontologie = Service de médecine Bucco-dentaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, 0301 basic medicine, bone marrow, Stromal cell, endocrine system diseases, Mice, Nude, Neovascularization, Physiologic, MSCs, 030209 endocrinology & metabolism, Biology, Article, Diabetes Mellitus, Experimental, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Thinness, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Downregulation and upregulation, Osteogenesis, ZDF, medicine, Animals, lcsh:QH301-705.5, Cell Proliferation, diabetes type 2, Mesenchymal stem cell, nutritional and metabolic diseases, Cell Differentiation, Mesenchymal Stem Cells, General Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Rats, Zucker, 3. Good health, stem cell, Transplantation, 030104 developmental biology, medicine.anatomical_structure, Diabetes Mellitus, Type 2, lcsh:Biology (General), Adipogenesis, Leukocytes, Mononuclear, Cancer research, Bone marrow, Stem cell
Abstract

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment, however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF, an obese-T2DM model) rats and their lean littermates (ZL, controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold, upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

Published
2021
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12. Molecular and cellular characterizations of human cherubism: disease aggressiveness depends on osteoclast differentiation

Author

Arnaud Picard, Quentin Sessiecq, Natacha Kadlub, Vianney Descroix, Amélie E. Coudert, Louise Galmiche, Cécile Badoual, Ariane Berdal, Aurore Coulomb L'Hermine, Marion Mandavit, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Physiopathologie orale moléculaire (CRC - Inserm U1138), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Service de chirurgie plastique et maxillofaciale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Trousseau - Service d׳Anatomie et Cytologie Pathologiques, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), UFR Odontologie [UPD7], Université Paris Diderot - Paris 7 (UPD7), Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Diderot - Paris 7 - UFR Odontologie (UPD7 Odontologie), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, 0301 basic medicine, Myeloid, medicine.medical_treatment, Osteoclasts, lcsh:Medicine, NFATc1, Osteogenesis, hemic and lymphatic diseases, Tumor Cells, Cultured, Pharmacology (medical), Child, Genetics (clinical), CD68, RANKL, Cell Differentiation, General Medicine, Middle Aged, Immunohistochemistry, Cytokine, medicine.anatomical_structure, Receptors, Tumor Necrosis Factor, Type I, Granuloma, Auto-inflammatory bone disease, Osteoclast, Female, Adult, musculoskeletal diseases, Adolescent, Biology, Young Adult, 03 medical and health sciences, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Vimentin, Adaptor Proteins, Signal Transducing, NFATC Transcription Factors, Interleukin-6, RANK Ligand, lcsh:R, Osteoprotegerin, Cherubism, medicine.disease, 030104 developmental biology, Giant cell, TNF-α, Mutation, Leukocytes, Mononuclear, biology.protein, Cancer research
Abstract

International audience; Background: Cherubism is a rare autosomal dominant disorder of the jaws caused by mutation of the SH3BP2 gene. The bone is replaced by a fibrous granuloma containing multinucleated giant cells. Cells of the cherubism granuloma have never been systematically analyzed. Hence, the aim of this study was to characterize the cells in human cherubism granulomas, to determine the osteoclastic characteristics of the multinucleated giant cells and to investigate the potential role of TNF-α in human cherubism.Results: Seven granulomas were analyzed in pathology, molecular biology and immunohistochemistry. Granulomas were composed mainly of macrophages or osteoclasts within a fibroblastic tissue, with few lymphoid cells. Myeloid differentiation and nuclear NFATc1 localization were both associated with disease aggressiveness. OPG and RANKL immunohistochemical expression was unexpected in our specimens. Five granuloma cells were cultured in standard and osteoclastogenic media. In culture, cherubism cells were able to differentiate into active osteoclasts, in both osteoclastogenic and standard media. IL-6 was the major cytokine present in the culture supernatants.Conclusion: Multinucleated giant cells from cherubism granulomas are CD68 positive cells, which differentiate into macrophages in non-aggressive cherubism and into osteoclasts in aggressive cherubism, stimulated by the NFATc1 pathway. This latter differentiation appears to involve a disturbed RANK-L/RANK/OPG pathway and be less TNF-α dependent than the cherubism mouse model.

Published
2018
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13. Effect of a hyperbaric environment (diving conditions) on adhesive restorations: an in vitro study

Author

Brigitte Grosgogeat, J Bosco, Nelly Pradelle-Plasse, C Mocquot, Pierre Colon, A Cabrera, Laboratoire des Multimatériaux et Interfaces (LMI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 - UFR Odontologie (UPD7 Odontologie), Université Paris Diderot - Paris 7 (UPD7), Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospices Civils de Lyon (HCL), UFR d’Odontologie, Université de Lyon, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], UFR Odontologie [UPD7], and Université de Lyon

Subjects
Materials science, medicine.medical_treatment, Composite number, Dental Cements, Dentistry, Dental bonding, Composite Resins, 03 medical and health sciences, 0302 clinical medicine, Dental cement, medicine, Humans, Dental Restoration, Permanent, Restorative dentistry, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, General Dentistry, ComputingMilieux_MISCELLANEOUS, Dental Leakage, Hyperbaric Oxygenation, business.industry, Dental Bonding, 030206 dentistry, medicine.disease, Resin Cements, Barodontalgia, Percolation, Adhesive, Dental Cavity Preparation, business, Dental restoration, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Objectives No recent study has addressed the effect of diving conditions (pressure increase) on adhesive restorations. We evaluated the impact of a simulated hyperbaric environment on microleakage of the dentine-composite resin interface. The ultimate aim was to propose recommendations for restorative dentistry for patients who are divers to limit barodontalgia (dental pain caused by pressure variations of the environment) and may lead to dangerous sequelae.Methods We bonded 20 dentine disks by using an adhesive system (Scothbond Universal) to ten intact composite cylinders and ten composite cylinders with porosity (Ceram X mono). For each group, the samples were divided into two subgroups, one submitted to a simulated hyperbaric environment and the other to an ambient environment. All samples were immersed in a silver nitrate solution to evaluate microleakage at the interface after analysis with a camera.Results Dye percolation for groups in the hyperbaric environment was greater than groups in ambient environment. For each subgroup, dye percolation was greater for samples with than without porosity.Conclusions High percolation percentages demonstrate that our simulated hyperbaric condition led to loss of sealing at the dentine-composite resin interface, especially with porous composites.Clinical significance Respect of the protocol and the quality of condensation for adhesive restorations are important in all clinical situations, especially for patients who are divers. A more interventionist approach must be adopted with these patients.

Published
2017
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14. Comparative Physicochemical Analysis of Pulp Stone and Dentin

Author

Fleur Beres, Ludovic Mouton, Stéphan Rouzière, Ariane Berdal, Stéphane Simon, Juliane Isaac, Arnaud Dessombz, Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), UFR d’Odontologie, Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Diderot - Paris 7 ( UPD7 ), Génétique Moléculaire de la Morphogénèse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Interfaces, Traitements, Organisation et Dynamique des Systèmes ( ITODYS UMR7086 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physique des Solides ( LPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Interfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS (UMR_7086)), Université Paris Diderot - Paris 7 (UPD7)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HAL-UPMC, Gestionnaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Service d'Odontologie = Service de médecine Bucco-dentaire [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, Male, 0301 basic medicine, Mineralized tissues, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Materials science, [ SDV.MHEP.AHA ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Root canal, Carious Dentin, Dentistry, Mineralization (biology), Apatite, 03 medical and health sciences, 0302 clinical medicine, X-Ray Diffraction, stomatognathic system, Metals, Heavy, Dentin, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Tooth Root, General Dentistry, Dental Pulp, Aged, Odontoblasts, business.industry, Spectrometry, X-Ray Emission, 030206 dentistry, Middle Aged, Pulp stone, Incisor, stomatognathic diseases, 030104 developmental biology, medicine.anatomical_structure, Odontoblast, visual_art, Microscopy, Electron, Scanning, visual_art.visual_art_medium, Dental Pulp Calcification, Female, Dental Pulp Cavity, business
Abstract

Introduction Odontoblasts are responsible for the synthesis of dentin throughout the life of the tooth. Tooth pulp tissue may undergo a pathologic process of mineralization, resulting in formation of pulp stones. Although the prevalence of pulp stones in dental caries is significant, their development and histopathology are poorly understood, and their precise composition has never been established. The aim of the present study was to investigate the physicochemical properties of the mineralized tissues of teeth to elucidate the pathologic origin of pulp stones. Methods Areas of carious and healthy dentin of 8 decayed teeth intended for extraction were analyzed and compared. In addition, 6 pulp stones were recovered from 5 teeth requiring root canal treatment. The samples were embedded in resin, sectioned, and observed by scanning electron microscopy and energy-dispersive spectroscopy. X-ray diffraction was performed to identify phases and crystallinity. X-ray fluorescence provided information on the elemental composition of the samples. Results Pulp stones showed heterogeneous structure and chemical composition. X-ray diffraction revealed partially carbonated apatite. X-ray fluorescence identified P, Ca, Cu, Zn, and Sr within dentin and pulp stones. Zn and Cu concentrations were higher in pulp stones and carious dentin compared with healthy dentin. Conclusions Pulpal cells produce unstructured apatitic mineralizations containing abnormally high Zn and Cu levels.

Published
2016
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15. Reduced susceptibility to amoxicillin of oral streptococci following amoxicillin exposure

Author

Jean Azérad, R. Toledo-Arenas, Vianney Descroix, C. Plainvert, Anne Bouvet, N. Nouacer, Kazutoyo Yasukawa, A. Ergani, Hélène Chardin, P. Aucouturier, Service d'Odontologie, Hôpital Albert Chenevier, AP-HP (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Service de Microbiologie-Hygiène, Hôpital de l'Hôtel-Dieu, Paris (AP-HP), Unité de Recherche Clinique et Centre Investigation Clinique-Epidémiologie, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d’Odontologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Microbiology (medical), Adult, medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], Antibiotics, Drug resistance, Microbial Sensitivity Tests, medicine.disease_cause, Microbiology, Gastroenterology, Drug Administration Schedule, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Antibiotic resistance, Internal medicine, Drug Resistance, Bacterial, medicine, Humans, Antibacterial agent, Odontogenic infection, 0303 health sciences, 030306 microbiology, business.industry, Streptococcus, Amoxicillin, 030206 dentistry, General Medicine, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, stomatognathic diseases, Oral microbiology, Tooth Extraction, business, medicine.drug
Abstract

International audience; As antibiotic pressure often triggers bacterial resistance, the use of short-duration therapies is increasingly recommended. The objective of the present study was to evaluate both the clinical efficiency and the impact on oral streptococci of a 3 day versus a 7 day amoxicillin therapy for odontogenic infection requiring tooth extraction. On day 0, patients were randomly assigned to a 3 day or 7 day amoxicillin treatment. The tooth was extracted on day 2 and the post-operative follow-up was carried out on day 9. Oral flora was collected on days 0, 9 and 30, and the susceptibility of the streptococci to amoxicillin was determined. The results showed that treatment with amoxicillin for 3 or 7 days had a similar clinical efficiency, and also induced similar selection of oral streptococci with reduced susceptibility to amoxicillin, suggesting that the selection of strains with reduced susceptibility to amoxicillin is a rapid phenomenon, appearing even with short-duration therapies.

Published
2009
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