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Article Dans Une Revue BioRxiv Année : 2024

Moesin activation controls bone resorption and tunneling nanotube-dependent osteoclast fusion

Ophélie Dufrancais
  • Fonction : Auteur
Perrine Verdys
  • Fonction : Auteur
Arnaud Métais
  • Fonction : Auteur
Marie Juzans
  • Fonction : Auteur
Thibaut Sanchez
  • Fonction : Auteur
Martin Bergert
  • Fonction : Auteur
Marianna Plozza
  • Fonction : Auteur
Julia Halper
  • Fonction : Auteur
Christopher Panebianco
Rémi Mascarau
  • Fonction : Auteur
Rémi Gence
Gaëlle Arnaud
  • Fonction : Auteur
Myriam Ben Neji
  • Fonction : Auteur
Isabelle Maridonneau-Parini
  • Fonction : Auteur
Véronique Le Cabec
  • Fonction : Auteur
Joel Boerckel
Nathan Pavlos
Alba Diz-Muñoz
Claudine Blin-Wakkach
Sébastien Carréno
Janis Burkhardt
Brigitte Raynaud-Messina
Christel Vérollet

Résumé

ABSTRACT Osteoclasts are multinucleated cells unique in their ability to resorb bone. Osteoclastogenesis involves several steps of actin-driven rearrangements that participate not only in the cell-cell fusion process, but also in the formation of the sealing zone, the adhesive structure determining the resorption area. Despite the importance of these actin cytoskeleton-based processes, their precise mechanisms of regulation are still poorly characterized. Here, we found that moesin, a member of the Ezrin/Radixin/Moesin (ERM) protein family, is activated during osteoclast maturation and plays an instrumental role for both osteoclast fusion and function. In mouse and human osteoclast precursors, moesin is negatively regulated to potentiate their ability to fuse and degrade bone. Accordingly, we demonstrated that moesin depletion decreases membrane-to-cortex attachment and enhances formation of tunneling nanotubes (TNTs), F-actin-containing intercellular bridges that we revealed to trigger osteoclast fusion. In addition, via a β3-integrin/RhoA/SLK pathway and independently of its role in fusion, moesin regulates the number and organization of sealing zones in mature osteoclast, and thus participates in the control of bone resorption. Supporting these findings, we found that moesin-deficient mice are osteopenic with a reduced density of trabecular bones and increased osteoclast abundance and activity. These findings provide a better understanding of the regulation of osteoclast biology, and open new opportunities to specifically target osteoclast activity in bone disease therapy.

Dates et versions

hal-04639892 , version 1 (09-07-2024)

Identifiants

Citer

Ophélie Dufrancais, Perrine Verdys, Arnaud Métais, Marie Juzans, Thibaut Sanchez, et al.. Moesin activation controls bone resorption and tunneling nanotube-dependent osteoclast fusion. BioRxiv, 2024, ⟨10.1101/2024.05.13.593799⟩. ⟨hal-04639892⟩
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