{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T18:52:13Z","timestamp":1762541533446},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[1998,3,1]],"date-time":"1998-03-01T00:00:00Z","timestamp":888710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Disintegrins are small disulfide-rich proteins containing an Arg-Gly-Asp (RGD) sequence near their carboxyl terminus. These polypeptides inhibit binding of adhesion molecules to their receptors (integrins) on the surface of cells. Osteoclasts express integrins, heterodimeric cell surface adhesion receptors, that have been shown to be involved in interactions with the extracellular matrix (ECM), including attachment to bone and bone resorption. It has recently been shown that disintegrins effectively inhibit attachment of osteoclasts to components of the ECM and also disrupt osteoclast-mediated bone resorption. Here we characterize the effects of contortrostatin (CTS), a novel homodimeric snake venom disintegrin, on osteoclast attachment. Plastic dishes coated with CTS were able to support osteoclast attachment with a high affinity (EC50,CTS = 86 \u00b1 6.7 nM) similar to that of vitronectin (VTN; EC50,VTN = 80 \u00b1 20 nM). Further, CTS was observed to inhibit completely osteoclast attachment to fetal bovine serum (FBS; IC50,FBS = 0.36 \u00b1 0.04 nM) and VTN (IC50,VTN = 0.85 \u00b1 0.13 nM). We used monoclonal antibodies directed against the \u03b21 (monoclonal antibody [MAb] CD29) and \u03b23 (MAb F11) integrin subunits to explore the mechanism of osteoclast attachment to immobilized CTS. Only MAb F11 inhibited attachment to immobilized CTS (IC50 = 0.41 \u00b1 0.12 \u03bcg\/ml), suggesting that binding to CTS is mediated in part by a \u03b23 integrin, presumably the \u03b1v\u03b23 VTN receptor. In further support of an integrin-mediated mechanism, binding of osteoclasts to CTS is inhibited by the RGD peptide, GRGDSP. CTS was also more potent (IC50,FBS = 0.36 \u00b1 0.04 nM) at inhibiting osteoclast attachment to FBS-coated wells than the monomeric snake venom disintegrin echistatin (IC50,FBS = 8.9 \u00b1 1.5 nM) or VTN (IC50,FBS = 97.5 \u00b1 25.5 nM). Taken together, these data suggest that the snake venom disintegrin CTS is a potent inhibitor of \u03b23 integrin-mediated osteoclast attachment, presumably involving the VTN receptor (an \u03b1v\u03b23 integrin). Further studies of the mechanism of CTS\u2013osteoclast interactions may aid in the design of peptide mimetics to act as antiresorptive agents for the treatment of osteoporosis and other skeletal pathology.<\/jats:p>","DOI":"10.1359\/jbmr.1998.13.3.409","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T19:57:46Z","timestamp":1146081466000},"page":"409-414","source":"Crossref","is-referenced-by-count":16,"title":["Contortrostatin, a Homodimeric Snake Venom Disintegrin, Is a Potent Inhibitor of Osteoclast Attachment"],"prefix":"10.1093","volume":"13","author":[{"given":"B.","family":"Mercer","sequence":"first","affiliation":[{"name":"Skeletal Biology Research Laboratory and Department of Basic Sciences, School of Dentistry, University of Southern California, Los Angeles, California, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Markland","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, University of Southern California, Los Angeles, California, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Minkin","sequence":"additional","affiliation":[{"name":"Skeletal Biology Research Laboratory and Department of Basic Sciences, School of Dentistry, University of Southern California, Los Angeles, California, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024020713314893500_bib1","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1002\/jbmr.5650090917","article-title":"Structure-activity studies of the s-Echistatin inhibition of bone resorption","volume":"9","author":"Sato","year":"1994","journal-title":"J Bone Miner Res"},{"key":"2024020713314893500_bib2","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/jbmr.5650090313","article-title":"Effects of Kistrin on bone-resorption 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