Moesin Protein Controls Bone Remodeling by Regulating Osteoclast Fusion and Function
Researchers at the Institut de Pharmacologie et Biologie Structurale (IPBS) have uncovered a pivotal role for the protein moesin in regulating bone remodeling. Their study, published in the Journal of Cell Biology, reveals that moesin controls both the fusion of bone-resorbing cells called osteoclasts and their ability to degrade bone. This discovery opens new avenues for understanding and potentially treating bone diseases such as osteoporosis.
Moesin: A Key Regulator of Osteoclast Fusion and Bone Resorption
Osteoclasts are specialized cells responsible for breaking down bone tissue, a process essential for bone remodeling and repair. However, excessive osteoclast activity can lead to bone loss and diseases like osteoporosis. The new study, led by Dr. Christel Vérollet and Dr. Brigitte Raynaud-Messina, demonstrates that moesin, a protein that links the actin cytoskeleton to the cell membrane, plays a critical role in controlling osteoclast function.
The researchers discovered that osteoclasts form tunneling nanotubes (TNTs), thin, actin-rich bridges that connect cells, during their early differentiation These TNTs facilitate the fusion of osteoclast precursors into multinucleated cells, which are more efficient at resorbing bone. Moesin acts as a brake on this process: when moesin is depleted, the number of TNTs increases, leading to enhanced cell fusion and the formation of larger, more active osteoclasts.
Moesin also helps control how osteoclasts attach to bone. When moesin is missing, actin adherent structures are bigger and more numerous, causing the bone to break down faster. The study shows that moesin’s activity is regulated by a specific chain of signals inside the cell, which helps keep bone resorption in check.
Figure: In the absence of moesin, human osteoclasts exhibit supernumerary nuclei (pink). Actin is shown in white. © Ophélie Dufrançais
To confirm their findings, the researchers analyzed mice lacking moesin. These mice exhibited reduced bone density and increased osteoclast activity, mirroring the effects observed in cell culture experiments. This suggests that moesin is essential for maintaining healthy bone structure and preventing excessive bone loss.
A New Target for Bone Disease Therapies
This research provides a deeper understanding of the molecular mechanisms underlying osteoclast function and bone resorption. By identifying moesin as a key regulator of osteoclast fusion, the study opens the door to novel therapeutic strategies for diseases characterized by excessive bone loss, such as osteoporosis and inflammatory bone disorders.
“Our findings highlight cell fusion and moesin as promising targets for modulating osteoclast activity”, said Dr. Vérollet. “By specifically targeting osteoclast-specific regulators of moesin, we may be able to develop treatments that prevent bone loss without disrupting other cellular processes”.
The study was conducted in collaboration with researchers from the Université Côte d’Azur/CNRS (LP2M), the European Molecular Biology Laboratory (EMBL), and the Université de Perth (Australia), as well as other international partners. It was supported by grants from the Agence Nationale de la Recherche (ANR) and the Fondation pour la Recherche Médicale.
Reference
Ophélie Dufrancais, Marianna Plozza, Marie Juzans, Arnaud Métais, Sarah C Monard, Pierre-Jean Bordignon, Perrine Verdys, Thibaut Sanchez, Martin Bergert, Julia Halper, Christopher J Panebianco, Rémi Mascarau, Rémi Gence, Gaëlle Arnaud, Myriam Ben Neji, Isabelle Maridonneau-Parini, Véronique Le Cabec, Joel D Boerckel, Nathan J Pavlos, Alba Diz-Muñoz, Frédéric Lagarrigue, Claudine Blin-Wakkach, Sébastien Carréno, Renaud Poincloux, Janis K Burkhardt, Brigitte Raynaud-Messina* and Christel Vérollet*. (2025) Moesin controls cell-cell fusion and osteoclast function. J Cell Biol DOI. 10.1083/jcb.202409169
Contact Scientist: Christel Vérollet | christel.verollet@ipbs.fr
Contact Press: Françoise Viala | Communication@ipbs.fr