Moesin controls cell–cell fusion and osteoclast function
Cell-cell fusion is an evolutionarily conserved process that is essential for many functions, including the formation of bone-resorbing multinucleated osteoclasts. Osteoclast multinucleation involves dynamic interactions between the actin cytoskeleton and the plasma membrane that are still poorly characterized. We found that moesin, a cytoskeletal linker protein member of the Ezrin, radixin, and moesin (ERM) protein family, plays a critical role in both osteoclast fusion and function. Moesin inhibition favors osteoclast multinucleation as well as HIV-1- and inflammation-induced cell fusion. Accordingly, moesin depletion decreases membrane-to-cortex attachment and enhances the formation of tunneling nanotubes, F-actin-based intercellular bridges triggering cell-cell fusion. In addition, moesin regulates the formation of the sealing zone, a key structure determining osteoclast bone resorption area, and thus controls bone degradation via a β3-integrin/RhoA/SLK pathway. Finally, moesin-deficient mice have reduced bone density and increased osteoclast abundance and activity. These findings provide a better understanding of cell-cell fusion and osteoclast biology, opening new opportunities to specifically target osteoclasts in bone disease therapy.
Authors
- Nathan J. Pavlos (ORCID: https://orcid.org/0000-0001-7003-188X)
- Thibaut Sanchez (ORCID: https://orcid.org/0000-0003-3087-8132)
- Renaud Poincloux (ORCID: https://orcid.org/0000-0003-2884-1744)
- Christopher J. Panebianco (ORCID: https://orcid.org/0000-0001-8683-5743)
- Pierre‐Jean Bordignon (ORCID: https://orcid.org/0000-0003-4073-8117)
- Isabelle Maridonneau‐Parini (ORCID: https://orcid.org/0000-0003-0189-0976)
- Gaëlle Arnaud (ORCID: https://orcid.org/0009-0005-1615-1553)
- Véronique Le Cabec (ORCID: https://orcid.org/0000-0002-0204-0976)
- Christel Vérollet (ORCID: https://orcid.org/0000-0002-1079-9085)
- Joel D. Boerckel (ORCID: https://orcid.org/0000-0003-3126-3025)
- Rémi Gence (ORCID: https://orcid.org/0000-0003-0747-3540)
- Martin Bergert (ORCID: https://orcid.org/0000-0002-3222-8929)
- Sarah Monard (ORCID: https://orcid.org/0000-0001-7149-312X)
- Myriam Ben Neji (ORCID: https://orcid.org/0009-0008-7414-349X)
- Janis K. Burkhardt (ORCID: https://orcid.org/0000-0002-8176-1375)
- Rémi Mascarau (ORCID: https://orcid.org/0000-0002-7009-2786)
- Ophélie Dufrançais (ORCID: https://orcid.org/0009-0006-0993-547X)
- Marie Juzans (ORCID: https://orcid.org/0009-0004-7665-8930)
- Claudine Blin‐Wakkach (ORCID: https://orcid.org/0000-0002-2621-3907)
- Sébastien Carreno (ORCID: https://orcid.org/0000-0002-5839-2102)
- Alba Diz-Muñoz (ORCID: https://orcid.org/0000-0001-6864-8901)
- Arnaud Métais (ORCID: https://orcid.org/0000-0002-9538-0338)
- Frédéric Lagarrigue (ORCID: https://orcid.org/0000-0002-4660-8666)
- Perrine Verdys (ORCID: https://orcid.org/0009-0002-4365-9895)
- Marianna Plozza (ORCID: https://orcid.org/0009-0008-5489-5360)
- Julia Halper (ORCID: https://orcid.org/0000-0003-3967-6633)
- Brigitte Raynaud-Messina (ORCID: https://orcid.org/0009-0000-1512-0871)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Children's Hospital of Philadelphia (US)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- The University of Western Australia (AU)
- Centre de Recherches en Cancérologie de Toulouse (FR)
- Laboratoire de PhysioMédecine Moléculaire (FR)
- Institut universitaire du cancer de Toulouse Oncopole (FR)
- Institut de Pharmacologie et de Biologie Structurale (FR)
- Institut de Recherche en Informatique de Toulouse (FR)
- European Molecular Biology Laboratory (DE)
- Bioengineering Center (RU)
- European Molecular Biology Laboratory (DE)
- Université de Montréal (CA)
- University of Pennsylvania (US)
Publication Details
- Journal
- The Journal of Cell Biology
- Published
- 2025-08-20
- DOI
- https://doi.org/10.1083/jcb.202409169
- Citations
- 6
- Primary Topic
- Bone Metabolism and Diseases
- Type
- article
- Field-Weighted Citation Impact
- 4.84