{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T22:28:38Z","timestamp":1770503318483,"version":"3.49.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"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":[[2000,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The proto-oncogene c-src, which encodes a non\u2013receptor-type tyrosine kinase c-Src, has been shown to be essential for osteoclastic bone resorption by the finding that the targeted disruption of the c-src gene induced osteopetrosis in mice. The csk (C-terminal Src family kinase) gene encodes a cytoplasmic protein-tyrosine kinase that specifically phosphorylates the negative regulatory site of c-Src (Tyr-527), thereby inhibiting its kinase activity. To regulate osteoclast function by modulating the kinase activity of c-Src, we constructed an adenovirus vector that carries this gene. The recombinant adenovirus vector carrying csk cDNA induced Csk expression in mouse osteoclast-like cells formed in vitro and clearly reduced c-Src kinase activity in a dose-dependent manner. The expression of Csk caused cytoskeletal disorganization of osteoclast-like cells and strongly suppressed pit-forming activity of the cells in vitro. In addition, the viral vector carrying csk gene dramatically suppressed interleukin-1\u03b1\u2013induced bone resorption in vivo. Conversely, kinase-inactive Csk caused an increase in c-Src kinase activity and bone resorbing activity of the cells both in vitro and in vivo, acting as a dominant negative molecule against intrinsic Csk. These findings indicate that the inhibition of c-Src activity by adenovirus vector-mediated csk expression offers an efficient means for inhibiting pathological bone resorption by suppressing osteoclast function.<\/jats:p>","DOI":"10.1359\/jbmr.2000.15.1.41","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T01:45:01Z","timestamp":1146102301000},"page":"41-51","source":"Crossref","is-referenced-by-count":33,"title":["In Vitro and In Vivo Suppression of Osteoclast Function by Adenovirus Vector\u2013Induced <i>csk<\/i> Gene"],"prefix":"10.1093","volume":"15","author":[{"given":"Tsuyoshi","family":"Miyazaki","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Takayanagi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Isshiki","sequence":"additional","affiliation":[{"name":"Fourth Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tokiharu","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Okada","sequence":"additional","affiliation":[{"name":"Division of Protein Metabolism, Institute for Protein Research, Osaka University, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhisa","family":"Fukui","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Chemistry, Department of Applied Biological Chemistry, Faculty of Agricultural and Life Science, University 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