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Effects of kistrin on bone resorption in vitro and serum calcium in vivo.

Abstract
In many cell systems, cell-cell and cell-matrix interactions are mediated by integrins, a family of cell surface heterodimeric glycoprotein receptors. Osteoclast integrins may play a role in the process of bone resorption. Osteoclasts express the alpha v and beta 3 subunits of the vitronectin receptor and adhere to a wide range of proteins in vitro, all which contain the amino acid sequence Arg-Gly-Asp (RGD), an adhesion site recognition sequence common to many protein ligands that bind to integrins. The effect of kistrin, an RGD-containing snake venom protein, on osteoclast-mediated bone resorption was investigated in vivo and in vitro. When kistrin was infused into normocalcemic and hypercalcemic mice, serum calcium was significantly lowered at 3 and 6 h after the start of infusion, indicating an inhibitory effect on osteoclast activity in vivo. In vitro, kistrin potently inhibited bone resorption by isolated rat osteoclasts cultured on slices of bovine bone, and kistrin also inhibited the attachment of 293 cells expressing recombinant human alpha v beta 3 to fibrinogen (IC50 = 1 nM). These results indicate the potential therapeutic use of RGD-containing molecules for hypercalcemia of malignancy or for other disorders associated with bone loss.
AuthorsK L King, J J D'Anza, S Bodary, R Pitti, M Siegel, R A Lazarus, M S Dennis, R G Hammonds Jr, S C Kukreja
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 9 Issue 3 Pg. 381-7 (Mar 1994) ISSN: 0884-0431 [Print] UNITED STATES
PMID8191932 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Crotalid Venoms
  • Oligopeptides
  • Peptides
  • kistrin
  • Fibrinogen
  • arginyl-glycyl-aspartic acid
  • Calcium
Topics
  • Amino Acid Sequence
  • Animals
  • Bone Resorption (physiopathology)
  • Calcium (blood)
  • Cell Adhesion (drug effects)
  • Cell Line
  • Cells, Cultured
  • Crotalid Venoms (pharmacology, therapeutic use)
  • Dose-Response Relationship, Drug
  • Fibrinogen (metabolism)
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Scanning
  • Molecular Sequence Data
  • Oligopeptides (pharmacology)
  • Osteoclasts (drug effects, physiology)
  • Peptides (chemistry, pharmacology, therapeutic use)
  • Rats

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