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

被引:109
作者
Chellaiah, MA [1 ]
Hruska, KA
机构
[1] Univ Maryland, Dept Oral & Craniofacial Biol Sci, Baltimore, MD 21201 USA
[2] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
关键词
osteoclasts; osteopontin; integrin alpha(v)beta(3); CD44; motility;
D O I
10.1007/s00223-002-1025-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In the studies reported here we demonstrate that osteopontin is secreted from the basolateral surfaces of osteoclasts where it binds to the alpha(v)beta(3)-integrin, suggesting that it may be an autocrine factor. Osteopontin stimulation of osteoclasts produced changes in cell shape by causing disruption of peripheral podosorne 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 alpha(v)beta(3) 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 alpha(v)beta(3) and CD44 during stimulation of osteoclast migration.
引用
收藏
页码:197 / 205
页数:9
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  • [1] ANALYSIS OF FIBRONECTIN RECEPTOR FUNCTION WITH MONOCLONAL-ANTIBODIES - ROLES IN CELL-ADHESION, MIGRATION, MATRIX ASSEMBLY, AND CYTOSKELETAL ORGANIZATION
    AKIYAMA, SK
    YAMADA, SS
    CHEN, WT
    YAMADA, KM
    [J]. JOURNAL OF CELL BIOLOGY, 1989, 109 (02) : 863 - 875
  • [2] ALBERTS B, 1994, CYTOSKELETON MOL BIO, P828
  • [3] Peptidomimetic antagonists of αvβ3 inhibit bone resorption by inhibiting osteoclast bone resorptive activity, not osteoclast adhesion to bone
    Carron, CP
    Meyer, DM
    Engleman, VW
    Rico, JG
    Ruminski, PG
    Ornberg, RL
    Westlin, WF
    Nickols, GA
    [J]. JOURNAL OF ENDOCRINOLOGY, 2000, 165 (03) : 587 - 598
  • [4] Gelsolin deficiency blocks podosome assembly and produces increased bone mass and strength
    Chellaiah, M
    Kizer, N
    Silva, M
    Alvarez, U
    Kwiatkowski, D
    Hruska, KA
    [J]. JOURNAL OF CELL BIOLOGY, 2000, 148 (04) : 665 - 678
  • [5] Osteopontin stimulates gelsolin-associated phosphoinositide levels and phosphatidylinositol triphosphate-hydroxyl kinase
    Chellaiah, M
    Hruska, K
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1996, 7 (05) : 743 - 753
  • [6] c-Src is required for stimulation of gelsolin-associated phosphatidylinositol 3-kinase
    Chellaiah, M
    Fitzgerald, C
    Alvarez, U
    Hruska, K
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (19) : 11908 - 11916
  • [7] CHELLAIAH M, 2002, IN PRESS MOL BIOL CE
  • [8] Rho-A is critical for osteoclast podosome organization, motility, and bone resorption
    Chellaiah, MA
    Soga, N
    Swanson, S
    McAllister, S
    Alvarez, U
    Wang, DM
    Dowdy, SF
    Hruska, KA
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (16) : 11993 - 12002
  • [9] Osteopontin
    Chellaiah, MA
    Hruska, KA
    [J]. DRUG NEWS & PERSPECTIVES, 1998, 11 (06) : 350 - 355
  • [10] Phosphatidylinositol 3,4,5-trisphosphate directs association of Src homology 2-containing signaling proteins with gelsolin
    Chellaiah, MA
    Biswas, RS
    Yuen, D
    Alvarez, UM
    Hruska, KA
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (50) : 47434 - 47444