{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:08:46Z","timestamp":1762927726293},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,2,19]],"date-time":"2004-02-19T00:00:00Z","timestamp":1077148800000},"content-version":"vor","delay-in-days":3397,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[1994,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bone resorption requires the tight attachment of the bone\u2010resorbing cells, the osteoclasts, to the bone mineralized matric. 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\u2010glycyl\u2010aspartyl (R\u2010G\u2010D) tripeptide present within the ligand sequence. The interaction between integrins and ligaands results in bidirectional transfer of signals across the plasma Membrane. Tyrosine phosphorylaation occurs within cells as a result of integrin binding to ligaands and probably plays a role in the formation of the osteoclast clear zone, a specialized region of the osteoclast membraane maintained by cytoskeletal structure and involved in bone resorption.<\/jats:p><jats:p>Human osteoclasts express \u03b1<jats:sub>2<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub> and \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub> integrins on their surface. Such signaling may also lead to \u201cinside\u2010out\u201d effects, like increased expression of integrin receptors on the cell surface, or increased affinity of the integrin to its ligand. The \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub> integrin, a vitronectin receptor, plays an essential role in bone resorption. Antibodies to this integrin and short synthetic RGD\u2010containing peptides are able to block bone resorption in vitro. Echistatin, an RGD\u2010containing protein from a snake venom, binds to the \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub> integrin and blocks bone resssorption both in vitro and in vivo. Peptides containing the RGD motif are potential competitive \u201cantagonists\u201d a of the osteoclast integrins and may have utility in the blockage of bone resorption. Agonists may be identified by stimulation of intracellularsignaling. In theory, tissue spacificity can be achieved by (1) introducing specific amino acids in positions adjacent to the RGD sequence, (2) identifying non\u2010RGD integrin binding domains, or (3) modulating the affinity of integrins for their endogenous ligands.<\/jats:p>","DOI":"10.1002\/jcb.240560308","type":"journal-article","created":{"date-parts":[[2005,5,28]],"date-time":"2005-05-28T21:50:14Z","timestamp":1117317014000},"page":"323-330","source":"Crossref","is-referenced-by-count":30,"title":["Blockade of osteoclast\u2010mediated bone resorption through occupancy of the integrin receptor: A potential approach to the therapy of osteoporosis"],"prefix":"10.1002","volume":"56","author":[{"given":"Rivka","family":"Dresner\u2010Pollak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Rosenblatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,2,19]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"9725","DOI":"10.1016\/S0021-9258(18)98408-5","article-title":"Site\u2010directed mutagenesis of the arginine\u2010glycine\u2010aspartic acid in vitronectin abolishes cell adhesion","volume":"268","author":"Cherny RC","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.4.1817"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1210\/endo.132.3.8440195","article-title":"Inhibition of osteoclastic bone resorption in vivo by echistatin, an \u201cagrinyl\u2010glycyl\u2010aspartyl\u201d (RGD)\u2010containing protein","volume":"132","author":"Fisher JE","year":"1993","journal-title":"Endocrinology"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"19827","DOI":"10.1016\/S0021-9258(19)77710-2","article-title":"Echistatin: A potent platelet aggregation inhibitor from the venom of the viper, Echis carinatus","volume":"263","author":"Gan Z\u2010R","year":"1988","journal-title":"J Biol Chem"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-0038-1642555","article-title":"Cytoadhesions, integrins, and platelets","volume":"59","author":"Ginsberg MH","year":"1988","journal-title":"Thromb Haemost"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00102a020"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3685994"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(91)90386-9"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"16157","DOI":"10.1016\/S0021-9258(18)47710-1","article-title":"Trigramin: a low molecular weight peptide inhibiting fibrinogen interaction with platelet receptors expressed on glycoprotein IIb\u2010IIIa complex","volume":"262","author":"Huang T\u2010F","year":"1987","journal-title":"J Biol Chem"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650080503"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.103.6.2637"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90115-S"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/40.8.1619274"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.115.4.1179"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.82.1.261"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90580-6"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.12.4473"},{"key":"e_1_2_1_19_1","doi-asserted-by":"crossref","first-page":"9901","DOI":"10.1016\/S0021-9258(18)98430-9","article-title":"Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alphavbeta3 potentiate bone resorption","volume":"268","author":"Ross FP","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2821619"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.111.4.1713"},{"key":"e_1_2_1_22_1","doi-asserted-by":"crossref","first-page":"11766","DOI":"10.1016\/S0021-9258(19)38464-9","article-title":"Binding of the snake venom\u2010derived proteins applaggin and echistatin to the arginineglycine\u2010aspartic acid recognition site(s) on platelet glycoprotein IIb. 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