{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:09:01Z","timestamp":1790352541699,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"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":[[2005,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We show that mice lacking \u03b23 integrin are protected from OVX-induced bone loss. Using a lentiviral-based strategy to express \u03b23 mutants in \u03b23\u2212\/\u2212 mice, we also show that \u03b23S752, but not \u03b23Y747\/Y759, is important for osteoclastic bone resorption in vivo.<\/jats:p>\n                  <jats:p>Introduction: Mice lacking the \u03b23 integrin have dysfunctional osteoclasts and therefore accumulate bone mass with age. Thus, the \u03b1v\u03b23 integrin is a potential anti-osteoporosis target. Identifying components of the \u03b23 integrin that determine its function in vivo is essential for therapeutically exploiting the antiresorptive properties of \u03b1v\u03b23.<\/jats:p>\n                  <jats:p>Materials and Methods: We used DXA and histomorphometry to assess bone loss after ovariectomy in wildtype and \u03b23 integrin null mice. We used lentiviral vectors carrying various human \u03b23 (h\u03b23) integrin constructs to transduce \u03b23\u2212\/\u2212 bone marrow and reconstituted lethally irradiated \u03b23\u2212\/\u2212 mice with the transduced marrow. The expressed constructs include the intact integrin and two mutants, namely h\u03b23Y747F\/Y759F and h\u03b23S752P, each of which induces the bleeding dyscrasia, Glanzmann's thrombasthenia, in humans. Two months after transplantation, the expression of h\u03b23 was measured by flow cytometry of marrow-derived macrophages. Osteoclast differentiation and function were assessed ex vivo by TRACP and actin-ring staining, respectively. Reconstituted mice were ovariectomized, and bone loss was assessed by DXA, histomorphometry, and serum TRACP5b assay.<\/jats:p>\n                  <jats:p>Results: \u03b23\u2212\/\u2212 mice are protected from ovariectomy-induced bone loss, showing no difference in BMD compared with sham-operated controls. We successfully expressed h\u03b23 integrins in \u03b23\u2212\/\u2212 hosts using lentiviral transduction of bone marrow. Two months after transplantation, 25\u201335% of marrow-derived macrophages expressed the h\u03b23 constructs. Similar to its effect in vitro, h\u03b23WT completely rescued the osteoclast and platelet phenotype of \u03b23\u2212\/\u2212 mice. Whereas platelet function remained deranged in \u03b23\u2212\/\u2212 mice overexpressing h\u03b23Y747F\/Y759F, osteoclast function was fully restored. In contrast, \u03b23\u2212\/\u2212 mice expressing h\u03b23S752P continued to exhibit prolonged bleeding times and dysfunctional osteoclasts in vitro and ex vivo. Most importantly, h\u03b23WT and h\u03b23Y747F\/Y759F transplanted mice underwent equivalent ovariectomy-induced bone loss, whereas, like those bearing the control vector, h\u03b23S752P transplanted mice were protected.<\/jats:p>\n                  <jats:p>Conclusions: Functional \u03b23 integrin is required for ovariectomy-induced bone loss. \u03b23S752, but not \u03b23Y747\/Y759, is critical for osteoclast function in vivo.<\/jats:p>","DOI":"10.1359\/jbmr.050724","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T20:51:42Z","timestamp":1146084702000},"page":"2116-2123","source":"Crossref","is-referenced-by-count":55,"title":["Critical Role of \u03b23 Integrin in Experimental Postmenopausal Osteoporosis"],"prefix":"10.1093","volume":"20","author":[{"given":"Haibo","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, 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