{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:57:40Z","timestamp":1791172660294,"version":"4.1.0"},"reference-count":37,"publisher":"The Company of Biologists","issue":"22","license":[{"start":{"date-parts":[[1999,11,15]],"date-time":"1999-11-15T00:00:00Z","timestamp":942624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The \u03b1v\u03b23 integrin is abundantly expressed in osteoclasts and has been implicated in the regulation of osteoclast function, especially in cell attachment. However, in vivo studies have shown that echistatin, an RGD-containing disintegrin which binds to \u03b1v\u03b23, inhibits bone resorption without changing the number of osteoclasts on the bone surface, suggesting inhibition of osteoclast activity. The objective of this study was to examine how occupancy of \u03b1v\u03b23 integrins inhibits osteoclast function, using primary rat osteoclasts and murine pre-fusion osteoclast-like cells formed in a co-culture system. We show that: (1) echistatin inhibits bone resorption in vitro at lower concentrations (IC50 = 0.1 nM) than those required to detach osteoclasts from bone (IC50 \u223c1 \u00b5M); (2) echistatin (IC50 = 0.1 nM) inhibits M-CSF-induced migration and cell spreading of osteoclasts; (3) \u03b1v\u03b23 integrins are localized in podosomes at the leading edge of migrating osteoclasts, whereas, with echistatin treatment (0.1 nM), \u03b1v\u03b23 disperses randomly throughout the adhesion surface; and (4) when bone resorption is fully inhibited with echistatin, there is visible disruption of the sealing zone (IC50 = 13 nM), and \u03b1v\u03b23 visualized with confocal microscopy re-distributes from the basolateral membranes to intracellular vesicular structures. Taken together, these findings suggest that \u03b1v\u03b23 integrin plays a role in the regulation of two processes required for effective osteoclastic bone resorption: cell migration (IC50 = 0.1 nM) and maintenance of the sealing zone (IC50 \u223c10 nM).<\/jats:p>","DOI":"10.1242\/jcs.112.22.3985","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T17:28:52Z","timestamp":1619371732000},"page":"3985-3993","source":"Crossref","is-referenced-by-count":182,"title":["Role of \u03b1v\u03b23 integrin in osteoclast migration and formation of the sealing zone"],"prefix":"10.1242","volume":"112","author":[{"given":"Ichiro","family":"Nakamura","sequence":"first","affiliation":[{"name":"1 Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary F.","family":"Pilkington","sequence":"additional","affiliation":[{"name":"The University of Western Ontario 2 Department of Physiology, Faculty of Medicine & Dentistry , , London, Ontario, Canada, N6A 5C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4ivi T.","family":"Lakkakorpi","sequence":"additional","affiliation":[{"name":"University of Turku 3 Department of Anatomy, Institute of Biomedicine , , Kiinamyllynkatu 10, FIN-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Lipfert","sequence":"additional","affiliation":[{"name":"1 Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Sims","sequence":"additional","affiliation":[{"name":"The University of Western Ontario 2 Department of Physiology, Faculty of Medicine & Dentistry , , London, Ontario, Canada, N6A 5C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Jeffrey","family":"Dixon","sequence":"additional","affiliation":[{"name":"The University of Western Ontario 2 Department of Physiology, Faculty of Medicine & Dentistry , , London, Ontario, Canada, N6A 5C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon A.","family":"Rodan","sequence":"additional","affiliation":[{"name":"1 Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le T.","family":"Duong","sequence":"additional","affiliation":[{"name":"1 Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1999,11,15]]},"reference":[{"key":"2024041523311244200_JOCES_112_22_3985C1","first-page":"127","article-title":"Monoclonal antibodies against osteoclasts inhibit bone resorption in vitro","volume":"1","author":"Chambers","year":"1986","journal-title":"Bone Miner"},{"key":"2024041523311244200_JOCES_112_22_3985C2","first-page":"1149","article-title":"Osteocalcin induces chemotaxis, secretion of matrix proteins and calcium- mediated intracellular signaling in human osteoclast-like cells","volume-title":"J. 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