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

Roberta Faccio, Maria Grano, Silvia Colucci, Antonello Villa, Gianluigi Giannelli, Vito Quaranta, Alberta Zallone

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Integrins are membrane receptors that mediate interactions between cells and the extracellular matrix. We recently showed that the osteoclast integrin αvβ3 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 αvβ3 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 αvβ3 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 αvβ3 conformation in vitro. Preincubation with HGF or M-CSF induces a shift of conformation of αvβ3 in primary human osteoclasts (OCs) and in the osteoclast-like cell line (GCT 23). Activated integrin promotes osteoclast migration to the αvβ3 ligand osteopontin and enhances bone resorption. Thus, HGF and M-CSF modulate the αvβ3 conformational states required for osteoclast polarization and resorption. The capacity of growth factors to alter the affinity of αvβ3 toward its ligands offers a potential explanation for the diverse responses of osteoclasts to the same ligand.

Original languageEnglish
Pages (from-to)2919-2929
Number of pages11
JournalJournal of cell science
Volume115
Issue number14
StatePublished - Jul 15 2002
Externally publishedYes

Keywords

  • Alpha v beta 3
  • HGF
  • Integrin
  • M-CSF
  • Osteoclasts

Fingerprint Dive into the research topics of 'Localization and possible role of two different alpha v beta 3 integrin conformations in resting and resorbing osteoclasts'. Together they form a unique fingerprint.

  • Cite this

    Faccio, R., Grano, M., Colucci, S., Villa, A., Giannelli, G., Quaranta, V., & Zallone, A. (2002). Localization and possible role of two different alpha v beta 3 integrin conformations in resting and resorbing osteoclasts. Journal of cell science, 115(14), 2919-2929.