Localization and possible role of two different alpha v beta 3 integrin conformations in resting and resorbing osteoclasts.
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
Roberta
R
Department of Human Anatomy and Histology, University of Bari, Italy. faccio@pathology.wustl.edu
Grano
Maria
M
Colucci
Silvia
S
Villa
Antonello
A
Giannelli
Gianluigi
G
Quaranta
Vito
V
Zallone
Alberta
A
D000911:Antibodies, Monoclonal; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D001862:Bone Resorption / Q000139:chemically induced / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011487:Protein Conformation / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D017228:Hepatocyte Growth Factor; D039302:Integrin alphaVbeta3; D016173:Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms