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Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
CD44 and beta3 integrin organize two functionally distinct actin-based domains in osteoclasts.
Anne Chabadel1, Inmaculada Bañon-Rodríguez, David Cluet
1Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Ecole Normale Supérieure de Lyon, 69364 Lyon, France.
Molecular Biology of the Cell
|September 28, 2007
Summary
Osteoclasts (OCs) use actin belts for adhesion and contraction, with distinct domains. CD44 marks podosome cores, essential for OC function, but Wiskott Aldrich Syndrome Protein Interacting Protein (WIP) is crucial for a fully functional sealing zone.
Area of Science:
- Cell Biology
- Cytoskeleton Dynamics
- Osteoclast Biology
Background:
- Mature osteoclasts (OCs) form actin belts resembling sealing zones on nonmineralized substrates.
- These belts consist of podosomes, crucial for osteoclast function.
Purpose of the Study:
- To investigate the functional domains within the osteoclast actin belt.
- To identify novel markers and regulators of osteoclast podosome formation and sealing zone function.
Main Methods:
- Analysis of osteoclast actin cytoskeleton organization.
- Investigating the roles of CD44, beta3 integrin, Wiskott Aldrich Syndrome Protein (WASp), and Wiskott Aldrich Syndrome Protein Interacting Protein (WIP) in osteoclast adhesion and contraction.
- Utilizing WIP-/- osteoclasts to assess podosome and actin cloud formation.
Main Results:
- The osteoclast actin belt comprises two domains: CD44-linked podosome cores (adhesion) and beta3 integrin-associated actin clouds (adhesion and contraction).
- WIP-/- osteoclasts lack podosomes but retain actin clouds, showing diminished WASp expression, essential for podosome formation.
- CD44 is identified as a novel marker of OC podosome cores; its clustering restores podosome cores and WASp expression in WIP-/- OCs.
Conclusions:
- CD44 is a key regulator of osteoclast podosome core formation and function.
- While CD44 signaling can initiate sealing zone formation, WIP is indispensable for a fully functional sealing zone in osteoclasts.
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