Lack of Adiponectin Drives Hyperosteoclastogenesis in Lipoatrophic Mice.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_CB73EF97C8A9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Lack of Adiponectin Drives Hyperosteoclastogenesis in Lipoatrophic Mice.
Périodique
Frontiers in cell and developmental biology
Auteur(s)
Madel M.B., Fu H., Pierroz D.D., Schiffrin M., Winkler C., Wilson A., Pochon C., Toffoli B., Taïeb M., Jouzeau J.Y., Gilardi F., Ferrari S., Bonnet N., Blin-Wakkach C., Desvergne B., Moulin D.
ISSN
2296-634X (Print)
ISSN-L
2296-634X
Statut éditorial
Publié
Date de publication
2021
Peer-reviewed
Oui
Volume
9
Pages
627153
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
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.
Mots-clé
AMPK, adiponectin, bone marrow adiposity, cortical bone porosity, osteoclast
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/04/2021 16:25
Dernière modification de la notice
05/10/2021 6:13
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