Inhibition of osteoclastic bone resorption in vivo by echistatin, an "arginyl-glycyl-aspartyl" (RGD)-containing protein.
Osteoclastic bone resorption requires the formation of a tightly sealed compartment between the osteoclast and the mineralized bone matrix. This compartment functions as an extracellular "lysosome" which contains proteolytic enzymes and acids. Vitronectin receptors (VnR, integrin alpha v beta 3) displayed on the osteoclast cell surface may play a role in the attachment of osteoclasts to the resorption surface. VnR are known to bind to arginyl-glycyl-aspartyl (RGD)-containing matrix proteins and it has recently been reported that soluble peptides containing RGD sequences can block osteoclast attachment to bone and inhibit bone resorption in vitro. In this study echistatin, a naturally-occurring protein containing an RGD-sequence motif, was shown to completely inhibit osteoclast-mediated bone resorption in vivo. Echistatin or smaller derivative peptides may prove useful in the treatment of disorders characterized by excess bone resorption, such as osteoporosis and metastatic bone disease.
Fisher
J E
JE
Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486.
Caulfield
M P
MP
Sato
M
M
Quartuccio
H A
HA
Gould
R J
RJ
Garsky
V M
VM
Rodan
G A
GA
Rosenblatt
M
M
D000818:Animals; D001862:Bone Resorption / Q000473:pathology / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D016105:Parathyroidectomy; D010455:Peptides; D051381:Rats; D017207:Rats, Sprague-Dawley; D013965:Thyroidectomy; D014757:Viper Venoms / Q000494:pharmacology*
D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010281:Parathyroid Hormone; D010455:Peptides; D014757:Viper Venoms; C057986:echistatin; C047981:arginyl-glycyl-aspartic acid; D002118:Calcium