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1دورية أكاديمية
المؤلفون: Nham, Than‐Thuy, Guiho, Romain, Brion, Régis, Amiaud, Jérôme, Le Royer, Bénédicte Brounais, Gomez‐Brouchet, Anne, Rédini, Françoise, Bertin, Hélios
المصدر: Oral Diseases ; ISSN 1354-523X 1601-0825
الوصف: Objectives Investigation of the therapeutic effect of zoledronic acid (ZA) in a preclinical model of jaw osteosarcoma (JO). Materials and Methods The effect of 100 μg/kg ZA administered twice a week was assessed in a xenogenic mouse model of JO. The clinical (tumor growth, development of lung metastasis), radiological (bone microarchitecture by micro‐CT analysis), and molecular and immunohistochemical (TRAP, RANK/RANKL, VEGF, and CD146) parameters were investigated. Results Animals receiving ZA exhibited an increased tumor volume compared with nontreated animals (71.3 ± 14.3 mm 3 vs. 51.9 ± 19.9 mm 3 at D14, respectively; p = 0.06) as well as increased numbers of lung metastases (mean 4.88 ± 4.45 vs. 0.50 ± 1.07 metastases, respectively; p = 0.02). ZA protected mandibular bone against tumor osteolysis (mean bone volume of 12.81 ± 0.53 mm 3 in the ZA group vs. 11.55 ± 1.18 mm 3 in the control group; p = 0.01). ZA induced a nonsignificant decrease in mRNA expression of the osteoclastic marker TRAP and an increase in RANK/RANKL bone remodeling markers. Conclusion The use of bisphosphonates in the therapeutic strategy for JO should be further explored, as should the role of bone resorption in the pathophysiology of the disease.
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2دورية أكاديمية
المؤلفون: Madel, Maria Bernadette, Halper, Julia, Ibáñez, Lidia, Claire, Lozano, Rouleau, Matthieu, Boutin, Antoine, Mahler, Adrien, Pontier-Bres, Rodolphe, Ciucci, Thomas, Topi, Majlinda, Hue, Christophe, Amiaud, Jérôme, Iborra, Salvador, Sancho, David, Heymann, Dominique, Garchon, Henri Jean, Czerucka, Dorota, Apparailly, Florence, Duroux-Richard, Isabelle, Wakkach, Abdelilah, Blin-Wakkach, Claudine
المساهمون: Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré AP-HP, ANR-16-CE14-0030 Henri-Jean Garchon Henri-Jean GarchonFondation pour la Recherche Médicale ECO20160736019 Maria-Bernadette MadelAgence Nationale de la Recherche, Laboratory of Biochemistry-Hormonology, Société Française de Biologie des Tissus Minéralisés, Société Française de Rhumatol-ogie, UFR Simone Veil, Université Versailles-Saint-Quentin, Univer-sité Versailles-Saint-Quentin, National Institutes of Health, NIH, National Cancer Institute, NCI, Fondation Arthritis, American Society for Bone and Mineral Research, ASBMR, European Calcified Tissue Society, ECTS, Agence Nationale de la Recherche, ANR, (ANR-15-IDEX-01, ANR-16-CE14-0030), Fondation pour la Recherche Médicale, FRM, (ECO20160736019), Chung Hua University, CHU, (LP2M), Conseil Régional Provence-Alpes-Côte d'Azur, Société Française d'Hématologie, SFH, ANR-16-CE14-0030,ORIOS,Origine et rôle des ostéoclastes inflammatoires, nouvelles cibles thérapeutiques dans les maladies rhumatoïdes(2016)
المصدر: EISSN: 2050-084X ; eLife ; https://hal.science/hal-04068580Test ; eLife, 2023, 12, ⟨10.7554/eLife.82037⟩
مصطلحات موضوعية: [SDV]Life Sciences [q-bio]
الوصف: International audience ; Bone destruction is a hallmark of chronic inflammation, and bone-resorbing osteoclasts arising under such a condition differ from steady-state ones. However, osteoclast diversity remains poorly explored. Here, we combined transcriptomic profiling, differentiation assays and in vivo analysis in mouse to decipher specific traits for inflammatory and steady-state osteoclasts. We identified and validated the pattern-recognition receptors (PRR) Tlr2, Dectin-1, and Mincle, all involved in yeast recognition as major regulators of inflammatory osteoclasts. We showed that administration of the yeast probiotic Saccharomyces boulardii CNCM I-745 (Sb) in vivo reduced bone loss in ovariectomized but not sham mice by reducing inflammatory osteoclastogenesis. This beneficial impact of Sb is mediated by the regulation of the inflammatory environment required for the generation of inflammatory osteoclasts. We also showed that Sb derivatives as well as agonists of Tlr2, Dectin-1, and Mincle specifically inhibited directly the differentiation of inflammatory but not steady-state osteoclasts in vitro. These findings demonstrate a preferential use of the PRR-associated costimulatory differentiation pathway by inflammatory osteoclasts, thus enabling their specific inhibition, which opens new therapeutic perspectives for inflammatory bone loss.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36848406; hal-04068580; https://hal.science/hal-04068580Test; https://hal.science/hal-04068580/documentTest; https://hal.science/hal-04068580/file/elife-82037-v1.pdfTest; PUBMED: 36848406
الإتاحة: https://doi.org/10.7554/eLife.82037Test
https://hal.science/hal-04068580Test
https://hal.science/hal-04068580/documentTest
https://hal.science/hal-04068580/file/elife-82037-v1.pdfTest -
3دورية أكاديمية
المؤلفون: Panez-Toro, Isidora, Heymann, Dominique, Gouin, François, Amiaud, Jérôme, Heymann, Marie-Françoise, Córdova, Luis
المساهمون: Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Universidad de Chile = University of Chile Santiago (UCHILE), Institut de Cancérologie de l'Ouest Angers/Nantes (UNICANCER/ICO), UNICANCER, Department of Oncology and Metabolism Sheffield, UK, The University of Sheffield Sheffield, U.K., Centre Léon Bérard Lyon, Nantes Université (Nantes Univ), IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile (IMPACT), Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Universidad de Chile = University of Chile Santiago (UCHILE)-Universidad de Chile = University of Chile Santiago (UCHILE)
المصدر: ISSN: 1664-3224.
مصطلحات موضوعية: Total joint replacement, Periprosthetic osteolysis, Aseptic loosening, Osteoimmunology, Macrophage, Inflammation, Osteoclast, Innate immune system, [SDV]Life Sciences [q-bio]
الوصف: International audience ; Classically, particle-induced periprosthetic osteolysis at the implant–bone interface has explained the aseptic loosening of joint replacement. This response is preceded by triggering both the innate and acquired immune response with subsequent activation of osteoclasts, the bone-resorbing cells. Although particle-induced periprosthetic osteolysis has been considered a foreign body chronic inflammation mediated by myelomonocytic-derived cells, current reports describe wide heterogeneous inflammatory cells infiltrating the periprosthetic tissues. This review aims to discuss the role of those non-myelomonocytic cells in periprosthetic tissues exposed to wear particles by showing original data. Specifically, we discuss the role of T cells (CD3 + , CD4 + , and CD8 + ) and B cells (CD20 + ) coexisting with CD68 + /TRAP − multinucleated giant cells associated with both polyethylene and metallic particles infiltrating retrieved periprosthetic membranes. This review contributes valuable insight to support the complex cell and molecular mechanisms behind the aseptic loosening theories of orthopedic implants.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38106424; inserm-04501796; https://inserm.hal.science/inserm-04501796Test; https://inserm.hal.science/inserm-04501796/documentTest; https://inserm.hal.science/inserm-04501796/file/fimmu-14-1310262.pdfTest; PUBMED: 38106424; PUBMEDCENTRAL: PMC10722268
الإتاحة: https://doi.org/10.3389/fimmu.2023.1310262Test
https://inserm.hal.science/inserm-04501796Test
https://inserm.hal.science/inserm-04501796/documentTest
https://inserm.hal.science/inserm-04501796/file/fimmu-14-1310262.pdfTest -
4دورية أكاديمية
المؤلفون: Crenn, Vincent, Amiaud, Jérôme, Gomez-Brouchet, Anne, Potiron, Vincent, Gouin, François, Rosset, Philippe, Nail, Louis-Romée Le, Vidal, Luciano, Bertin, Helios, Brion, Régis, Tran, Guillaume, Verrecchia, Franck, Corre, Isabelle, Redini, Françoise
المساهمون: Sarcomes osseux et remodelage des tissus calcifiés - INSERM U1238 (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de Cancérologie de l'Ouest Angers/Nantes (UNICANCER/ICO), UNICANCER, Centre Léon Bérard Lyon, Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de Recherche en Génie Civil et Mécanique (GeM), Centre National de la Recherche Scientifique (CNRS)-NANTES UNIVERSITÉ - École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université - Institut Universitaire de Technologie Saint-Nazaire (Nantes Univ - IUT Saint-Nazaire), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - Ecole Polytechnique de l'Université de Nantes (Nantes Univ - EPUN)
المصدر: ISSN: 2156-6976 ; American Journal of Cancer Research ; https://cnrs.hal.science/hal-03862019Test ; American Journal of Cancer Research, 2022, 180, pp.105709.
مصطلحات موضوعية: Osteosarcoma, microenvironment, vascularization, chemotherapy, CD31, endomucin, α-SMA, immunohistochemistry, immunofluorescence, multiplexing, [SDV]Life Sciences [q-bio]
الوصف: International audience ; Predicting a response of osteosarcoma patients to chemotherapy, such as doxorubicin or high-dose methotrexate cocktail, remains a challenge in the clinic. Moreover, the prognostic value of currently used necrosis analysis is debatable. New markers of the therapeutic response or the prognostic response are urgently needed. The microenvironment plays a key role in the vascularization of highly heterogeneous tumors. Using the syngeneic MOS-J mouse model of osteosarcoma, we focused our study on the immunohistochemistry of tumor vascularization in order to identify new vessel markers, and to search for potential markers of the therapeutic response. Endomucin+, CD31+, and α-SMA+-positive elements were quantified in control (n=6) and doxorubicin-treated (n=6) mice in three different intra-tumor locations. We also used co-labeling to assess CD31+/Endomucin+ and CD31+/α-SMA+ co-expression. We identified a central tumor zone with a low vascularization profile for all of these markers. We identified two distinct types of vessels: CD31+/Endomucin+ vessels with a sprouting, neo-angiogenic, interlaced appearance, and CD31+/α-SMA+ vessel with a well-defined, mature structure. Doxorubicin appeared to reduce CD31+ expression in the tumor invasion front. In the doxorubicin-sensitive model, there were four times more CD31+/α-SMA+ elements than in the poorly responsive model. Therefore, we propose a methodology based on immunohistochemistry and multiplexed immunofluorescence to use endomucin as a promising new vascular marker in the osteosarcoma model. Moreover, our results suggest that CD31+/α-SMA+ vessels could be considered to be indicators of vasculature normalization and they may be used as specific markers of a good therapeutic response.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35530297; hal-03862019; https://cnrs.hal.science/hal-03862019Test; https://cnrs.hal.science/hal-03862019/documentTest; https://cnrs.hal.science/hal-03862019/file/ajcr0012-1843.pdfTest; PUBMED: 35530297; PUBMEDCENTRAL: PMC9077066
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5دورية أكاديمية
المؤلفون: Muñoz-Garcia, Javier, Vargas-Franco, Jorge William, Brounais-Le Royer, Benedicte, Cochonneau, Denis, Amiaud, Jérôme, Heymann, Marie-Francoise, Heymann, Dominique, Lezot, Frederic
المساهمون: Institut de Cancérologie de l'Ouest Angers/Nantes (UNICANCER/ICO), UNICANCER, Universidad de Antioquia = University of Antioquia Medellín, Colombia, Nantes Université (Nantes Univ), Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), University of Sheffield Sheffield, CHU Trousseau APHP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau APHP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
المصدر: ISSN: 2072-6694.
مصطلحات موضوعية: osteosarcoma, RANKL, endothelin, bone protection, metastases, [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], [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, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer
الوصف: International audience ; Current treatments for osteosarcoma, combining conventional polychemotherapy and surgery, make it possible to attain a five-year survival rate of 70% in affected individuals. The presence of chemoresistance and metastases significantly shorten the patient’s lifespan, making identification of new therapeutic tools essential. Inhibiting bone resorption has been shown to be an efficient adjuvant strategy impacting the metastatic dissemination of osteosarcoma, tumor growth, and associated bone destruction. Unfortunately, over-apposition of mineralized matrix by normal and tumoral osteoblasts was associated with this inhibition. Endothelin signaling is implicated in the functional differentiation of osteoblasts, raising the question of the potential value of inhibiting it alone, or in combination with bone resorption repression. Using mouse models of osteosarcoma, the impact of macitentan, an endothelin receptor inhibitor, was evaluated regarding tumor growth, metastatic dissemination, matrix over-apposition secondary to RANKL blockade, and safety when combined with chemotherapy. The results showed that macitentan has no impact on tumor growth or sensitivity to ifosfamide, but significantly reduces tumoral osteoid tissue formation and the metastatic capacity of the osteosarcoma. To conclude, macitentan appears to be a promising therapeutic adjuvant for osteosarcoma alone or associated with bone resorption inhibitors.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35406536; inserm-03625367; https://inserm.hal.science/inserm-03625367Test; https://inserm.hal.science/inserm-03625367/documentTest; https://inserm.hal.science/inserm-03625367/file/cancers-14-01765-v2.pdfTest; PUBMED: 35406536; PUBMEDCENTRAL: PMC8997105; WOS: 000781491000001
الإتاحة: https://doi.org/10.3390/cancers14071765Test
https://inserm.hal.science/inserm-03625367Test
https://inserm.hal.science/inserm-03625367/documentTest
https://inserm.hal.science/inserm-03625367/file/cancers-14-01765-v2.pdfTest -
6دورية أكاديمية
المؤلفون: Danieau, Geoffroy, Morice, Sarah, Renault, Sarah, Brion, Régis, Biteau, Kevin, Amiaud, Jérôme, Cadé, Marie, Heymann, Dominique, Lézot, Frédéric, Verrecchia, Franck, Rédini, Françoise, Brounais-Le Royer, Bénédicte
المساهمون: 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 = Nantes University Hospital (CHU Nantes)-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 = Nantes University Hospital (CHU Nantes), OSE Immunotherapeutics Nantes, École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL), Institut de Cancérologie de l'Ouest Angers/Nantes (UNICANCER/ICO), UNICANCER, Université de Nantes (UN), Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Department of Oncology and Metabolism Sheffield, UK, The University of Sheffield Sheffield, U.K.
المصدر: ISSN: 1424-8247 ; Pharmaceuticals ; https://hal.science/hal-04064240Test ; Pharmaceuticals, 2021, 14 (5), pp.421. ⟨10.3390/ph14050421⟩.
مصطلحات موضوعية: osteosarcoma, β-catenin, proliferation, migration, ICG-001, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
الوصف: International audience ; High-grade osteosarcomas are the most frequent malignant bone tumors in the pediatric population, with 150 patients diagnosed every year in France. Osteosarcomas are associated with low survival rates for high risk patients (metastatic and relapsed diseases). Knowing that the canonical Wnt signaling pathway (Wnt/β-catenin) plays a complex but a key role in primary and metastatic development of osteosarcoma, the aim of this work was to analyze the effects of ICG-001, a CBP/βcatenin inhibitor blocking the β-catenin dependent gene transcription, in three human osteosarcoma cell lines (KHOS, MG63 and 143B). The cell proliferation and migration were first evaluated in vitro after ICG-001 treatment. Secondly, a mouse model of osteosarcoma was used to establish the in vivo biological effect of ICG-001 on osteosarcoma growth and metastatic dissemination. In vitro, ICG-001 treatment strongly inhibits osteosarcoma cell proliferation through a cell cycle blockade in the G0/G1 phase, but surprisingly, increases cell migration of the three cell lines. Moreover, ICG-001 does not modulate tumor growth in the osteosarcoma mouse model but, rather significantly increases the metastatic dissemination to lungs. Taken together, these results highlight, despite an anti-proliferative effect, a deleterious pro-migratory role of ICG-001 in osteosarcoma.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34062831; hal-04064240; https://hal.science/hal-04064240Test; https://hal.science/hal-04064240/documentTest; https://hal.science/hal-04064240/file/pharmaceuticals-14-00421-v3.pdfTest; PUBMED: 34062831; PUBMEDCENTRAL: PMC8147379; WOS: 000654397300001
الإتاحة: https://doi.org/10.3390/ph14050421Test
https://hal.science/hal-04064240Test
https://hal.science/hal-04064240/documentTest
https://hal.science/hal-04064240/file/pharmaceuticals-14-00421-v3.pdfTest -
7دورية أكاديمية
المؤلفون: Gama, Andrea, Vargas-Franco, Jorge, William, Sánchez Mesa, Diana Carolina, Restrepo Bedoya, Elizabeth, Amiaud, Jérôme, Babajko, Sylvie, Berdal, Ariane, Acevedo, Ana Carolina, Heymann, Dominique, Lezot, Frederic, Castaneda, Beatriz
المساهمون: 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), 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 = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
المصدر: ISSN: 1661-6596.
مصطلحات موضوعية: tooth, RANKL/RANK signaling, Hertwig's epithelial root sheath, bone resorption, root formation, [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], [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, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer
الوصف: International audience ; 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.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/32209985; inserm-02529631; https://inserm.hal.science/inserm-02529631Test; https://inserm.hal.science/inserm-02529631/documentTest; https://inserm.hal.science/inserm-02529631/file/Gama%20et%20al%20Int%20J%20Mol%20Sci%202020.pdfTest; PUBMED: 32209985
الإتاحة: https://doi.org/10.3390/ijms21062201Test
https://inserm.hal.science/inserm-02529631Test
https://inserm.hal.science/inserm-02529631/documentTest
https://inserm.hal.science/inserm-02529631/file/Gama%20et%20al%20Int%20J%20Mol%20Sci%202020.pdfTest -
8دورية أكاديمية
المؤلفون: Maruelli, Silvia, Besio, Roberta, Rousseau, Julie, Garibaldi, Nadia, Amiaud, Jerome, Brulin, Benedicte, Layrolle, Pierre, Escriou, Virginie, Rossi, Antonio, Trichet, Valerie, Forlino, Antonella
المساهمون: Università degli Studi di Pavia = University of Pavia (UNIPV), 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 = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1267)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
المصدر: ISSN: 2590-0285 ; Matrix Biology Plus ; https://cnrs.hal.science/hal-03292038Test ; Matrix Biology Plus, 2020, 6, pp.100028. ⟨10.1016/j.mbplus.2020.100028⟩.
مصطلحات موضوعية: BCP, biphasic calcium phosphate, Collagen, D-MEM, Dulbecco-modified Eagle's medium, EDS, Ehlers Danlos syndrome, EGFP, enhanced green fluorescent protein, FBS, fetal bovine serum, Gene therapy, MEF, murine embryonic fibroblast, MSC, mesenchymal stem cell, NMD, nonsense mediated RNA decay, OI, osteogenesis imperfecta, PBS, phosphate buffered saline, RNAi, RNA interference, SDS, sodium dodecyl sulphate, Silencing, TRAP, tartrate-resistant acid phosphatase, shRNA
الوصف: International audience ; Classical osteogenesis imperfecta (OI) is an inherited rare brittle bone disease caused by dominant mutations in the COL1A1 or COL1A2 genes, encoding for the alpha chains of collagen type I. The definitive cure for the disease will require a gene therapy approach, aimed to correct or suppress the mutant allele. Interestingly, individuals lacking alpha2(I) chain and synthetizing collagen alpha1(I)3 homotrimers do not show bone phenotype, making appealing a bone specific COL1A2 silencing approach for OI therapy. To this aim, three different Col1a2-silencing RNAs (siRNAs), -3554, -3825 and -4125, selected at the 3'-end of the murine Col1a2 transcript were tested in vitro and in vivo. In murine embryonic fibroblasts Col1a2-siRNA-3554 was able to efficiently and specifically target the Col1a2 mRNA and to strongly reduce alpha2(I) chain expression. Its efficiency and specificity were also demonstrated in primary murine osteoblasts, whose mineralization was preserved. The efficiency of Col1a2-siRNA-3554 was proved also in vivo. Biphasic calcium phosphate implants loaded with murine mesenchymal stem cells were intramuscularly transplanted in nude mice and injected with Col1a2-siRNA-3554 three times a week for three weeks. Collagen alpha2 silencing was demonstrated both at mRNA and protein level and Masson's Trichrome staining confirmed the presence of newly formed collagen matrix. Our data pave the way for further investigation of Col1a2 silencing and siRNA delivery to the bone tissue as a possible strategy for OI therapy.
العلاقة: hal-03292038; https://cnrs.hal.science/hal-03292038Test; https://cnrs.hal.science/hal-03292038/documentTest; https://cnrs.hal.science/hal-03292038/file/hal-03292038.pdfTest
الإتاحة: https://doi.org/10.1016/j.mbplus.2020.100028Test
https://cnrs.hal.science/hal-03292038Test
https://cnrs.hal.science/hal-03292038/documentTest
https://cnrs.hal.science/hal-03292038/file/hal-03292038.pdfTest -
9دورية أكاديمية
المؤلفون: Mullard, Mathilde, Cadé, Marie, Morice, Sarah, Dupuy, Maryne, Danieau, Geoffroy, Amiaud, Jérome, Renault, Sarah, Lézot, Frédéric, Brion, Régis, Thepault, Rose, Anne, Ory, Benjamin, Lamoureux, François, Corre, Isabelle, Brounais-Leroyer, Bénédicte, Rédini, Françoise, Verrecchia, Franck
المساهمون: Sarcomes osseux et remodelage des tissus calcifiés - INSERM U1238 (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de Cancérologie de l'Ouest Angers/Nantes (UNICANCER/ICO), UNICANCER, Hôtel-Dieu de Nantes
المصدر: ISSN: 2072-6694.
مصطلحات موضوعية: GANT61, Gli1, SHH, ewing’s sarcoma, osteosarcoma, primary tumor growth, [SDV]Life Sciences [q-bio]
الوصف: International audience ; Osteosarcoma (OS) and Ewing’s sarcoma (ES) are the most common malignant bone tumors in children and adolescents. In many cases, the prognosis remains very poor. The Sonic hedgehog (SHH) signaling pathway, strongly involved in the development of many cancers, regulate transcription via the transcriptional factors Gli1-3. In this context, RNAseq analysis of OS and ES cell lines reveals an increase of some major compounds of the SHH signaling cascade in ES cells, such as the transcriptional factor Gli1. This increase leads to an augmentation of the transcriptional response of Gli1 in ES cell lines, demonstrating a dysregulation of Gli1 signaling in ES cells and thus the rationale for targeting Gli1 in ES. The use of a preclinical model of ES demonstrates that GANT61, an inhibitor of the transcriptional factor Gli1, reduces ES primary tumor growth. In vitro experiments show that GANT61 decreases the viability of ES cell, mainly through its ability to induce caspase-3/7-dependent cell apoptosis. Taken together, these results demonstrates that GANT61 may be a promising therapeutic strategy for inhibiting the progression of primary ES tumors.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33228057; inserm-04090341; https://inserm.hal.science/inserm-04090341Test; https://inserm.hal.science/inserm-04090341/documentTest; https://inserm.hal.science/inserm-04090341/file/cancers-12-03438-v2.pdfTest; PUBMED: 33228057; PUBMEDCENTRAL: PMC7699338; WOS: 000592949200001
الإتاحة: https://doi.org/10.3390/cancers12113438Test
https://inserm.hal.science/inserm-04090341Test
https://inserm.hal.science/inserm-04090341/documentTest
https://inserm.hal.science/inserm-04090341/file/cancers-12-03438-v2.pdfTest -
10دورية أكاديمية
المؤلفون: Suliman, Salwa, Ali, Hassan Mohamed Abdel-Raouf, Karlsen, Tommy Aleksander, Amiaud, Jérôme, Mohamed Ahmed, Samih, Layrolle, Pierre, Costea, Daniela Elena, Brinchmann, Jan E., Mustafa, Kamal Babikeir Eln
المصدر: Scientific Reports
الوصف: Therapeutic potential of human bone marrow stromal/stem cells (hBMSC) must be developed using well defined xenogenic-free conditions. hBMSC were isolated from healthy donors (n = 3) using different isolation and expansion methods. Donor I was isolated and expanded by either bone marrow directly seeded and cells expanded in 10% AB human serum (AB) +5 ng/ml fibroblast growth factor-2 (FGF2) [Direct(AB + FGFlow)] or Ammonium-Chloride-Potassium Lysing Buffer was used before the cells were expanded in 10% AB +5 ng/ml FGF-2 [ACK(AB + FGFlow)] or Lymphoprep density gradient medium was used before the cells were expanded in 10% AB +5 ng/ml FGF2 [Lympho(AB + FGFlow)] or bone marrow directly seeded and cells expanded in 10% pooled platelet lysate plasma (PL) + heparin (2 I/U/mL) [Direct(PL)]. Groups for donors II and III were: Direct(AB + FGFlow) or 10% AB +10 ng/ml FGF2 [Direct(AB + FGFhigh)] or Direct(PL). HBMSCs were assessed for viability, multi-potency, osteogenic, inflammatory response and replicative senescence in vitro after 1 and 3 weeks. Pre-selected culture conditions, Direct(AB + FGFhigh) or Direct(PL), were seeded on biphasic calcium phosphate granules and subcutaneously implanted in NOD/SCID mice. After 1 and 11 weeks, explants were analysed for inflammatory and osteogenic response at gene level and histologically. To identify implanted human cells, in situ hybridisation was performed. hBMSC from all conditions showed in vitro multi-lineage potency. hBMSCs expanded in PL expressed stemness markers in vitro at significantly higher levels. Generally, cells expanded in AB + FGF2 conditions expressed higher osteogenic markers after 1 week both in vitro and in vivo. After 11 weeks in vivo, Direct(AB + FGFhigh) formed mature ectopic bone, compared to immature mineralised tissues formed by Direct(PL) implants. Mouse responses showed a significant upregulation of IL-1α and IL-1β expression in Direct(PL). After 1 week, human cells were observed in both groups and after 11 weeks in Direct(AB + FGFhigh) only. To ...
وصف الملف: application/pdf
العلاقة: urn:issn:2045-2322; https://hdl.handle.net/1956/23583Test; https://doi.org/10.1038/s41598-019-52442-9Test; cristin:1760633
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