CD44 and β3 Integrin Organize Two Functionally Distinct Actin-based Domains in Osteoclasts
Open accessAbstract
The actin cytoskeleton of mature osteoclasts (OCs) adhering to nonmineralized substrates is organized in a belt of podosomes reminiscent of the sealing zone (SZ) found in bone resorbing OCs. In this study, we demonstrate that the belt is composed of two functionally different actin-based domains: podosome cores linked with CD44, which are involved in cell adhesion, and a diffuse cloud associated with β3 integrin, which is involved in cell adhesion and contraction. Wiskott Aldrich Syndrome Protein (WASp) Interacting Protein (WIP)−/− OCs were devoid of podosomes, but they still exhibited actin clouds. Indeed, WIP−/− OCs show diminished expression of WASp, which is required for podosome formation. CD44 is a novel marker of OC podosome cores and the first nonintegrin receptor detected in these structures. The importance of CD44 is revealed by showing that its clustering restores podosome cores and WASp expression in WIP−/− OCs. However, although CD44 signals are sufficient to form a SZ, the presence of WIP is indispensable for the formation of a fully functional SZ.
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These osteoclast membrane domains are only formed when osteoclasts are in contact with extracellular mineralized matrix, in a process in which αvβ3-integrin and CD44 mediate the attachment of osteoclast podosomes to the bone surface.
“It is important to mention that these domains are only formed when osteoclasts are in contact with extracellular mineralized matrix, in a process which α v β 3-integrin, as well as the CD44, mediates the attachment of the osteoclast podosomes to the bone surface [96–99].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [99]
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- Authors
- Chabadel, A., Bañon-Rodríguez, I., Cluet, D., Rudkin, B. B., Wehrle-Haller, B., Genot, E., Jurdic, P., Anton, I. M., & Saltel, F.
- Affiliations
- Lyon 1 Université (FR)
- Centro de Biología Molecular “Severo Ochoa,” Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid, 28049 Madrid, Spain;
- Department of Cellular Physiology and Metabolism, Centre Médical Universitaire, 1211 Geneva 4, Switzerland; and
- Inserm (FR)
- Consejo Superior de Investigaciones Científicas (ES)
- Venue
- Molecular Biology of the Cell
- Published
- 2007-12
- Volume
- 18
- Issue
- 12
- Pages
- 4899-4910
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2096584
- OpenAlex
- W2160358447
- Cited by
- 154
- References
- 57
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 6 · 2020: 13 · 2019: 10 · 2018: 9 · 2017: 3 · 2016: 8 · 2015: 8 · 2014: 11 · 2013: 7 · 2012: 11
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- HAL (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- European Social Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- osteoclasts, CD44, CD61, actin cytoskeleton, podosomes, sealing zone, WIP, wasps, cell adhesion, bone resorption, receptor clustering
- MeSH terms
- Actins, Animals, Bone Resorption, Intracellular Membranes, Osteoclasts, Signal Transduction, Mice, Knockout, Hyaluronan Receptors, Integrin beta3, Wiskott-Aldrich Syndrome Protein, Mice
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