The integrin αvβ3 and CD44 regulate the actions of osteopontin on osteoclast motility

M. A. Chellaiah, K. A. Hruska

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

In the studies reported here we demonstrate that osteopontin is secreted from the basolateral surfaces of osteoclasts where it binds to the αvβ3-integrin, suggesting that it may be an autocrine factor. Osteopontin stimulation of osteoclasts produced changes in cell shape by causing disruption of peripheral podosome structures and formation of actin filaments at the leading edge of the migrating osteoclasts. The latter was part of the assumption of a motile phenotype prior to cells reforming peripheral ring type podosome containing clear zones. It is well established in our laboratory as well as in others that osteopontin stimulated osteoclast motility and bone resorption. The effect of osteopontin was mimicked by RGD containing peptides and blocked by a αvβ3 antibody, demonstrating that signals generated by integrin ligation contributed to the actions of osteopontin. In addition, the migratory effects of osteopontin on osteoclasts were also mediated through CD44 receptors since blocking antibodies to CD44 blocked stimulation of motility. Our data strongly suggest that osteopontin is an osteoclast autocrine motility factor binding to αvβ3 and CD44 during stimulation of osteoclast migration.

Original languageEnglish
Pages (from-to)197-205
Number of pages9
JournalCalcified Tissue International
Volume72
Issue number3
DOIs
StatePublished - Mar 1 2003

Keywords

  • CD44
  • Integrin αβ
  • Motility
  • Osteoclasts
  • Osteopontin

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