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J Cell Biochem. 1994 Nov;56(3):323-30.

Blockade of osteoclast-mediated bone resorption through occupancy of the integrin receptor: a potential approach to the therapy of osteoporosis.

Author information

1
Thorndike Laboratory, Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02215.

Abstract

Bone resorption requires the tight attachment of the bone-resorbing cells, the osteoclasts, to the bone mineralized matrix. Integrins, a class of cell surface adhesion glycoproteins, play a key role in the attachment process. Most integrins bind to their ligands via the arginyl-glycyl-aspartyl (R-G-D) tripeptide present within the ligand sequence. The interaction between integrins and ligands results in bidirectional transfer of signals across the plasma membrane. Tyrosine phosphorylation occurs within cells as a result of integrin binding to ligands and probably plays a role in the formation of the osteoclast clear zone, a specialized region of the osteoclast membrane maintained by cytoskeletal structure and involved in bone resorption. Human osteoclasts express alpha 2 beta 1 and alpha v beta 3 integrins on their surface. Such signaling may also lead to "inside-out" effects, like increased expression of integrin receptors on the cell surface, or increased affinity of the integrin to its ligand. The alpha v beta 3 integrin, a vitronectin receptor, plays an essential role in bone resorption. Antibodies to this integrin and short synthetic RGD-containing peptides are able to block bone resorption in vitro. Echistatin, an RGD-containing protein from a snake venom, binds to the alpha v beta 3 integrin and blocks bone resorption both in vitro and in vivo. Peptides containing the RGD motif are potential competitive "antagonists" of the osteoclast integrins and may have utility in the blockade of bone resorption. Agonists may be identified by stimulation of intracellular signaling.(ABSTRACT TRUNCATED AT 250 WORDS).

PMID:
7876325
DOI:
10.1002/jcb.240560308
[Indexed for MEDLINE]
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