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Marrow Adiposity and Bone Lab - MABLab

Marrow Adiposity and Bone Lab - MABLab. Activités :. Humain. A. Relations Adipo Méd et qualité/quantité osseuse en contextes pathologiques : ostéoporose liée à âge, ménopause, obésité, diabète, anorexie, arthrose. B. Régulations et activités des Adipo Méd

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Marrow Adiposity and Bone Lab - MABLab

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  1. Marrow Adiposity and Bone Lab - MABLab Activités : Humain A. Relations AdipoMéd et qualité/quantité osseuse en contextes pathologiques : ostéoporose liée à âge, ménopause, obésité, diabète, anorexie, arthrose. B. Régulations et activités des AdipoMéd C. Développement d’outils spécifiques pour l’analyse ostéomédullaire Animal In vitro Personnel : 8 U, 8 H, 9 ITA 1

  2. Partenariatsrecherche Partenariatscliniques • A POLONI (Univ. Ancona) • Boulogne/Mer Hospital • F PATTOU(CHU, EGID Univ. Lille) • R COURSIER (Lille CatholicHospital) • MH LAFAGE-PROUST (Inserm 1059, St Etienne) • W CAWTHORN (Edinburgh Univ.) • G KERCKHOFS (KU Leuven & CatholicUniv. Louvain) • X HOUARD (Inserm 5938, Paris) Collaborations cliniquesrégionales: CHU Lille via les cliniciens du labo : rhumatologie, chirurgieorthop., radiologie, odontologie GHICL via 2 cliniciens du labo : rhumatologie et radiologie Projetenémergence avec CH Boulogne : cf Damien Leterme

  3. Relationships between BMAT and bone quality/quantity in pathological situations • Osteoporosis in anorexianervosa: • experimentalmodels (in vivo)  Implication of adipokines complexrelationshipBMA/BW loss • (ex vivo)  Adipogenesis   osteogenesis/mineralisation • clinicalstudies leptinemiaand adiponectinemia are linkedwithbonestatus

  4. A. Relationships between BMAT and bone quality/quantity in pathological situations 2. Postmenopausal osteoporosis: - Potential impact of BMAT variation on bone quality. - Modification in a site specific manner (hip, knee, mandible, vertebrae)

  5. A. Relationships between BMAT and bone quality/quantity in pathological situations 3. Osteo-articular diseases: - Femoral Head OsteoNecrosis clinical studies  Subchondral plaque alteration but no modification of trabecular bone  Specific distribution of the BMAT (DIXON and µCT) - Osteoarthritis experimental models (in vivo)  development of a mouse model (DMM: next contract project) - BMAT perfusion MRI evaluation (Dynamic-Contrast Enhanced) of microvasculature  development of a tool for clinical studies

  6. B. Cellular characterization and activities of bone marrow adipocytes • Phenotype and functional specificities of medullar adipocytes - in the ovariectomy mouse model (4 and 14wks) BM adipocytes are characterized by high expression levels of RANKL and Wnt inhibitors; BM adipocyte phenotype evolves with bone loss and glucose intolerance worsening. - in human MSC-derived adipocytes Chronic culture in high glucose  sFRP4 expression. 25mM glucose 10 100 µm 5 5mM 0 0 7 14 21 3 100 µm Visceral Ad Femur & tibia BM Ad relative expression of sFRP4 time (days)

  7. B. Cellular characterization and activities of bone marrow adipocytes 2. BM adipocyte influences osteoblastogenesis Co-culture Adipo / osteo Human MSCs • Productssecreted by adipocytes induceosteoblasts to differentiatetowards an adipocyte phenotype 48h Differentomics data : secretome and transcriptome (3 and 7 biologicalreplicates, respectively)

  8. B. Cellular characterization and activities of bone marrow adipocytes 3. Lipids in mineralized bone and in bone marrow • Validation of the extraction method from mineral and in marrow • Distinct lipid content in both compartments • Characterization of specific lipids associated with mineral matrix

  9. C. Specific tool development for osteo-medullar analysis • BMAT analysis (µCT-CE, DIXON, histology) • Lipid analysis (TLC/HPLC, Raman) • Perfusion assessment (MRI, CE) • In vitro model (co-culture, co-differentiation) • Co-localization

  10. Development of international collaborations • Team’s contribution to structuration of BMAT research • ANR BONEAHEAD (BONE Adiposity in HEAlth and Diseases) • COST applications • ETN applications • BMAS creation2017 (WGs with white papers preparation) • BMA2015 & BMA 2018 (Next BMA congresses in Denmark and USA) • Relationship with industry (Servier, MSD Avenir) • Obesity diabetes (LabExEgid)

  11. New project of teamNew ambitionsStrong focus New name! • Scientific objectives: to achieve a global understanding of BMAT and bone relationships thanks to strengthened mechanistic approaches within different contexts and through two main questions: • What are the key regulators of BMA according to the physiological situation? • By which mechanisms are bone marrow adipocytes involved in bone pathology and energetic metabolism? Marrow Adiposity and Bone Lab - MABLab LaboratoireAdipositéMédullaire et Os - LAMOs • HCERES demand: EA renewal / single team / single thematic

  12. Structuration of the mains axes of the 2020-2024 project Board: Dir., Ass. Dir., Axis coordinators Relationshipsbetweenbone and bonemarrowadiposity Axis 1 J Paccou Axis 2 S Lucas Axis 3 T Pascart Osteoporosisrelated to menopause and to ageing Osteoporosisrelated to metabolicalterations Subchondralbone in osteonecrosis and osteoarthritis Bonefragility and regulation of adipogenesis and osteoblastogenesis in anorexianervosa Fat and vascularenvironment of bonemarrow Bonequality Bonefragility and functionalregulations of bonemarrow adipocyte in obesityand T2D Fracture risk Adipocyte secretions and osteoblastogenesis Local lipids and mineralisation Emergingprojects/ Mature projects

  13. Axis 1 Axis 2 Axis 3 Teams and main collaborations (basic researchers, physicians) Osteoporosisrelated to menopause and to ageing Osteoporosisrelated to metabolicalterations Subchondralbone in osteonecrosis and osteoarthritis J PACCOU (PU-PH) O BROUX (IR HDR) A CLABAUT (MCU) B CORTET (PU-PH) A DURING (MCU) D LETERME (MCU) C OLEJNIK (MCU-PH) G PENEL (PU-PH) S LUCAS (MCU) C CHAUVEAU (PU) B CORTET (PU-PH) A COTTEN (PU-PH) O GHALI (MCU) I LEGROUX-GEROT (PH) D LETERME (MCU) J PACCOU (PU-PH) G PASQUIER (PU-PH) H BENACHOUR (MCU) T PASCART (Clin) JF BUDZIK (Clin) O GHALI (MCU) D LETERME (MCU) S LUCAS (MCU) H MIGAUD (PU-PH) Researchers PMOI • Strong involvement of Physicians • Large sharing of specific methods thanks to IATSS • 1 PhD axis 1 + 2 PhD Axis 2 • 4 proposals for PhD support • Start funding for each Axis + 2 ANR proposals • Animal experiments: V GAUHTIER, F MIELLOT • Histology: S DELPLACE, V GAUHTIER, F MIELLOT • Microtomography: J DELATTRE, P MARCHANDISE • RAMAN Spectroscopy: G FALGAYRAC • Biologicalsamplepreparation: N BERTHEAUME • Secretariat: A GALET, MF LOUCHET IATSS PMOI • A POLONI (Univ. Ancona) • Boulogne/Mer Hospital • G KERCKHOFS (KU Leuven & CatholicUniv. Louvain) • W CAWTHORN (Edinburgh Univ.) • G KERCKHOFS (KU Leuven & CatholicUniv. Louvain) • F PATTOU, T HUBERT (EGID Univ. Lille) • R COURSIER (Lille CatholicHospital) • G KERCKHOFS (KU Leuven & CatholicUniv., Louvain) • X HOUARD (Inserm 5938, Paris) • MH LAFAGE-PROUST (Inserm 1059, St Etienne) Main collaborations

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