Interaction of osteopontin with osteoclast integrins.
Mammalian osteoclasts express three integrin receptors--alpha v beta 3 (vitronectin receptor), alpha 2 beta 1 and alpha v beta 1. The vitronectin receptor recognizes bone matrix proteins, including bone sialoproteins, in an RGD-dependent manner, whereas adhesion to collagen involves beta 1 integrins. Interference with integrin function, by anti-receptor antibodies or RGD-peptides, blocks bone resorption. Data on the mechanism of osteoclast adhesion to sialoproteins and the differential synthesis of osteopontin and bone sialoprotein by osteoclasts is presented. Thus, osteoclasts adhere to both osteopontin and bone sialoprotein with a characteristic irregular morphology with numerous, peripherally placed, actin-rich podosomes. Adhesion is predominantly RGD and beta 3 dependent, though alpha v beta 1 may also be involved in adhesion to bone sialoprotein. KQAGD and AGDV, but not H12, fibrinogen peptides induce osteoclast 'rounding' on osteopontin suggesting there is an alternative anti-adhesive signal to 'RGD.' However, adhesion is not completely inhibited and is not specific for osteopontin as equivalent effects are seen with adhesion to serum. The role of sialoproteins in osteoclast adhesion in situ in the skeleton is complicated by the finding of endogenous synthesis of osteopontin, but not bone sialoprotein, by osteoclasts. The disposition of osteoclast integrins during resorption and the role of integrins and sialoprotein-derived peptides in osteoclast adhesion and function is also reviewed.
Horton
M A
MA
Department of Medicine, University College London, Thorn Institute, Middlesex Hospital, England.
Nesbit
M A
MA
Helfrich
M H
MH
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D015870:Gene Expression; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D016023:Integrins / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000502:physiology*; D053495:Osteopontin; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D016024:Receptors, Cytoadhesin / Q000502:physiology*; D019030:Receptors, Vitronectin; D012795:Sialoglycoproteins / Q000378:metabolism / Q000502:physiology*
C546871:IBSP protein, human; C546872:Ibsp protein, mouse; C546873:Ibsp protein, rat; D058574:Integrin-Binding Sialoprotein; D016023:Integrins; D012333:RNA, Messenger; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; C506897:Spp1 protein, rat; D053495:Osteopontin