Integrins are membrane receptors that mediate interactions between cells and the extracellular matrix. We recently showed that the osteoclast integrin alpha(v)beta(3) exists in two different conformations, so-called 'basal' and 'activated', with each exhibiting a distinct function. In this study we demonstrate that, in non-resorbing osteoclasts, the 'activated' form of alpha(v)beta(3) accumulates in the motile areas of the plasma membrane. During bone resorption this conformation is prevalent in the ruffled membrane, whereas the 'basal' form of alpha(v)beta(3) is also present in the sealing zone. Moreover, hepatocyte growth factor (HGF) and macrophage colony stimulating factor (M-CSF), two molecules involved in osteoclastogenesis and osteoclast survival, modulate alpha(v)beta(3) conformation in vitro. Preincubation with HGF or M-CSF induces a shift of conformation of alpha(v)beta(3) in primary human osteoclasts (OCs) and in the osteoclast-like cell line (GCT 23). Activated integrin promotes osteoclast migration to the alpha(v)beta(3) ligand osteopontin and enhances bone resorption. Thus, HGF and M-CSF modulate the alpha(v)beta(3) conformational states required for osteoclast polarization and resorption. The capacity of growth factors to alter the affinity of alpha(v)beta(3) toward its ligands offers a potential explanation for the diverse responses of osteoclasts to the same ligand.

Faccio, R., Grano, M., Colucci, S., Villa, A., Giannelli, G., Quaranta, V., et al. (2002). Localization and possible role of two different alpha v beta 3 integrin conformations in resting and resorbing osteoclasts. JOURNAL OF CELL SCIENCE, 115(Pt 14), 2919-2929.

Localization and possible role of two different alpha v beta 3 integrin conformations in resting and resorbing osteoclasts

VILLA, ANTONELLO;
2002

Abstract

Integrins are membrane receptors that mediate interactions between cells and the extracellular matrix. We recently showed that the osteoclast integrin alpha(v)beta(3) exists in two different conformations, so-called 'basal' and 'activated', with each exhibiting a distinct function. In this study we demonstrate that, in non-resorbing osteoclasts, the 'activated' form of alpha(v)beta(3) accumulates in the motile areas of the plasma membrane. During bone resorption this conformation is prevalent in the ruffled membrane, whereas the 'basal' form of alpha(v)beta(3) is also present in the sealing zone. Moreover, hepatocyte growth factor (HGF) and macrophage colony stimulating factor (M-CSF), two molecules involved in osteoclastogenesis and osteoclast survival, modulate alpha(v)beta(3) conformation in vitro. Preincubation with HGF or M-CSF induces a shift of conformation of alpha(v)beta(3) in primary human osteoclasts (OCs) and in the osteoclast-like cell line (GCT 23). Activated integrin promotes osteoclast migration to the alpha(v)beta(3) ligand osteopontin and enhances bone resorption. Thus, HGF and M-CSF modulate the alpha(v)beta(3) conformational states required for osteoclast polarization and resorption. The capacity of growth factors to alter the affinity of alpha(v)beta(3) toward its ligands offers a potential explanation for the diverse responses of osteoclasts to the same ligand.
Articolo in rivista - Articolo scientifico
Integrin alphaVbeta3; Macrophage Colony-Stimulating Factor; Fluorescent Antibody Technique; Protein Conformation; 1-Phosphatidylinositol 3-Kinase; Humans; Enzyme Inhibitors; Protein Isoforms; Bone Resorption; Tumor Cells, Cultured; Bone and Bones; Antibodies, Monoclonal; Osteoclasts; Cell Movement; Hepatocyte Growth Factor; Bone Remodeling; Cell Membrane
English
2002
115
Pt 14
2919
2929
none
Faccio, R., Grano, M., Colucci, S., Villa, A., Giannelli, G., Quaranta, V., et al. (2002). Localization and possible role of two different alpha v beta 3 integrin conformations in resting and resorbing osteoclasts. JOURNAL OF CELL SCIENCE, 115(Pt 14), 2919-2929.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/18665
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