Academic Journal
Lack of Adiponectin Drives Hyperosteoclastogenesis in Lipoatrophic Mice
| العنوان: | Lack of Adiponectin Drives Hyperosteoclastogenesis in Lipoatrophic Mice |
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| المؤلفون: | Madel, Maria-Bernadette, Fu, He, Pierroz, Dominique, D, Schiffrin, Mariano, Winkler, Carine, Wilson, Anne, Pochon, Cécile, Toffoli, Barbara, Taïeb, Mahdia, Jouzeau, Jean- Yves, Gilardi, Federica, Ferrari, Serge, Bonnet, Nicolas, Blin-Wakkach, Claudine, Desvergne, Béatrice, Moulin, David |
| المساهمون: | Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics Lausanne (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Université de Lausanne = University of Lausanne (UNIL), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital Lausanne (CHUV), Nestlé Institute of Health Sciences SA Lausanne, Switzerland, This work was supported by the Etat de Vaud (BD and AW) the FNRS 31003A-135583/1 (BD), the Région Grand Est (J-YJ), the Fondation Arthritis (DM), the French PIA project Lorraine Université d’Excellence, reference ANR-15-IDEX-04-LUE (J-YJ and DM) and the Fondation pour la Recherche Médicale (FRM,ECO20160736019) (M-BM)., IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015) |
| المصدر: | ISSN: 2296-634X ; Frontiers in Cell and Developmental Biology ; https://hal.science/hal-03356534 ; Frontiers in Cell and Developmental Biology, 2021, 9, pp.627153. ⟨10.3389/fcell.2021.627153⟩. |
| بيانات النشر: | HAL CCSD Frontiers media |
| سنة النشر: | 2021 |
| المجموعة: | Université de Lorraine: HAL |
| مصطلحات موضوعية: | AMPK, adiponectin, bone marrow adiposity, cortical bone porosity, osteoclast, [SDV.BA]Life Sciences [q-bio]/Animal biology |
| الوصف: | International audience ; Long bones from mammals host blood cell formation and contain multiple cell types, including adipocytes. Physiological functions of bone marrow adipocytes are poorly documented. Herein, we used adipocyte-deficient PPARγ-whole body null mice to investigate the consequence of total adipocyte deficiency on bone homeostasis in mice. We first highlighted the dual bone phenotype of PPARγ null mice: one the one hand, the increased bone formation and subsequent trabecularization extending in the long bone diaphysis, due to the well-known impact of PPARγ deficiency on osteoblasts formation and activity; on the other hand, an increased osteoclastogenesis in the cortical bone. We then further explored the cause of this unexpected increased osteoclastogenesis using two independent models of lipoatrophy, which recapitulated this phenotype. This demonstrates that hyperosteoclastogenesis is not intrinsically linked to PPARγ deficiency, but is a consequence of the total lipodystrophy. We further showed that adiponectin, a cytokine produced by adipocytes and mesenchymal stromal cells is a potent inhibitor of osteoclastogenesis in vitro and in vivo . Moreover, pharmacological activation of adiponectin receptors by the synthetic agonist AdipoRon inhibited mature osteoclast activity both in mouse and human cells by blocking podosome formation through AMPK activation. Finally, we demonstrated that AdipoRon treatment blocks bone erosion in vivo in a murine model of inflammatory bone loss, providing potential new approaches to treat osteoporosis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/33869176; hal-03356534; https://hal.science/hal-03356534; https://hal.science/hal-03356534/document; https://hal.science/hal-03356534/file/627153_Manuscript-1.pdf; PUBMED: 33869176; PUBMEDCENTRAL: PMC8047205 |
| DOI: | 10.3389/fcell.2021.627153 |
| الاتاحة: | https://hal.science/hal-03356534 https://hal.science/hal-03356534/document https://hal.science/hal-03356534/file/627153_Manuscript-1.pdf https://doi.org/10.3389/fcell.2021.627153 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.9DA0F219 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fcell.2021.627153 |
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