{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:56:18Z","timestamp":1789592178234,"version":"build-2803163510"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2001,7,1]],"date-time":"2001-07-01T00:00:00Z","timestamp":993945600000},"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":[[2001,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Transforming growth factor-\u03b2 (TGF-\u03b2) is released from the matrix during bone resorption and has been implicated in the pathogenesis of giant cell tumors of bone and the expansion of breast cancer metastases in bone. Because osteoclasts mediate tumor-induced osteolysis, we investigated whether TGF-\u03b2 stimulates osteoclast recruitment. Osteoclasts were isolated from rat long bones and time-lapse video microscopy was used to monitor their morphology and motility. Within 5 minutes, TGF-\u03b2 (0.1 nM) induced dynamic ruffling, with 65% of osteoclasts displaying membrane ruffles compared with 35% in untreated controls. Over a 2-h period, osteoclasts exhibited significant directed migration toward a source of TGF-\u03b2, indicating chemotaxis. echistatin, an \u03b1v\u03b23 integrin blocker that inhibits macrophage colony-stimulating factor (M-CSF)-induced osteoclast migration, did not prevent the migration of osteoclasts toward TGF-\u03b2. In contrast, a \u03b21 integrin blocking antibody inhibited osteoclast chemotaxis toward TGF-\u03b2 but not M-CSF. These data indicate the selective use of integrins by osteoclasts migrating in response to different chemotaxins. In addition, wortmannin and U0126 inhibited TGF-\u03b2-induced chemotaxis, suggesting involvement of the phosphatidylinositol 3 (PI\u20093) kinase and mitogen-activated protein (MAP) kinase signaling pathways. Physiologically, TGF-\u03b2 may coordinate osteoclast activity by recruiting osteoclasts to existing sites of resorption. Pathologically, TGF-\u03b2-induced osteoclast recruitment may be critical for expansion of primary and metastatic tumors in bone.<\/jats:p>","DOI":"10.1359\/jbmr.2001.16.7.1237","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T04:29:33Z","timestamp":1146112173000},"page":"1237-1247","source":"Crossref","is-referenced-by-count":43,"title":["Transforming Growth Factor-\u03b2 Induces Osteoclast Ruffling and Chemotaxis: Potential Role in Osteoclast Recruitment"],"prefix":"10.1093","volume":"16","author":[{"given":"Mary F.","family":"Pilkington","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Sims","sequence":"additional","affiliation":[{"name":"Division of Oral Biology, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada"},{"name":"Department of Physiology, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Jeffrey","family":"Dixon","sequence":"additional","affiliation":[{"name":"Division of Oral Biology, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada"},{"name":"Department of Physiology, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024020714124970300_bib1","first-page":"647","volume-title":"Principles of Bone Biology","author":"Bonewald","year":"1996"},{"key":"2024020714124970300_bib2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/jbmr.5650090402","article-title":"Osteoclast synthesis and secretion and activation of latent transforming growth factor \u03b2","volume":"9","author":"Oursler","year":"1994","journal-title":"J Bone Miner 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