{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T14:40:35Z","timestamp":1776696035621,"version":"3.51.2"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T00:00:00Z","timestamp":1445299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR063049"],"award-info":[{"award-number":["AR063049"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Activation of Notch1 in osteocytes of <jats:italic>Rosa<jats:sup>Notch<\/jats:sup><\/jats:italic> mice, where a <jats:italic>loxP<\/jats:italic>\u2010flanked STOP cassette and the Nicd coding sequence were targeted to the reverse orientation splice acceptor (<jats:italic>Rosa<\/jats:italic>)<jats:italic>26<\/jats:italic> locus, causes osteopetrosis associated with suppressed <jats:italic>Sost<\/jats:italic> expression and enhanced Wnt signaling. To determine whether <jats:italic>Sost<\/jats:italic> downregulation mediates the effects of Notch activation in osteocytes, <jats:italic>Rosa<jats:sup>Notch<\/jats:sup><\/jats:italic> mice were crossed with transgenics expressing Cre recombinase or <jats:italic>SOST<\/jats:italic> under the control of the dentin matrix protein (<jats:italic>Dmp<\/jats:italic>)<jats:italic>1<\/jats:italic> promoter. <jats:italic>Dmp1\u2010SOST<\/jats:italic> transgenics displayed vertebral osteopenia and a modest femoral cancellous and cortical bone phenotype, whereas hemizygous <jats:italic>Dmp1\u2010Cre<\/jats:italic> transgenics heterozygous for the <jats:italic>Rosa<jats:sup>Notch<\/jats:sup><\/jats:italic> allele (<jats:italic>Dmp1\u2010Cre<\/jats:italic>;<jats:italic>Rosa<jats:sup>Notch<\/jats:sup><\/jats:italic>) exhibited osteopetrosis. The phenotype of Notch activation in osteocytes was prevented in <jats:italic>Dmp1\u2010Cre<\/jats:italic>;<jats:italic>Rosa<jats:sup>Notch<\/jats:sup><\/jats:italic> mice hemizygous for the <jats:italic>Dmp1\u2010SOST<\/jats:italic> transgene. The effect was associated with downregulated Notch signaling and suppressed <jats:italic>Dmp1<\/jats:italic> and <jats:italic>Rosa26<\/jats:italic> expression. To test whether SOST regulates Notch expression in osteocytes, cortical bone cultures from <jats:italic>Dmp1\u2010Cre<\/jats:italic>;<jats:italic>Rosa<jats:sup>Notch<\/jats:sup><\/jats:italic> mice or from <jats:italic>Rosa<jats:sup>Notch<\/jats:sup><\/jats:italic> control littermates were exposed to recombinant human SOST. The addition of SOST had only modest effects on Notch target gene mRNA levels and suppressed <jats:italic>Dmp1<\/jats:italic>, but not <jats:italic>Cre<\/jats:italic> or <jats:italic>Rosa26<\/jats:italic>, expression. These findings suggest that prevention of the <jats:italic>Dmp1\u2010Cre<\/jats:italic>;<jats:italic>Rosa<jats:sup>Notch<\/jats:sup><\/jats:italic> skeletal phenotype by <jats:italic>Dmp1\u2010SOST<\/jats:italic> is not secondary to SOST expression but to interactions among the <jats:italic>Dmp1\u2010SOST<\/jats:italic> and <jats:italic>Dmp1\u2010Cre<\/jats:italic> transgenes and the <jats:italic>Rosa26<\/jats:italic> locus. In conclusion, the <jats:italic>Dmp1\u2010SOST<\/jats:italic> transgene suppresses the expression of the <jats:italic>Dmp1\u2010Cre<\/jats:italic> transgene and of <jats:italic>Rosa26<\/jats:italic>. J. Cell. Biochem. 117: 1222\u20131232, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25405","type":"journal-article","created":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T03:07:12Z","timestamp":1444705632000},"page":"1222-1232","source":"Crossref","is-referenced-by-count":3,"title":["The <i>Dmp1\u2010SOST<\/i> Transgene Interacts With and Downregulates the <i>Dmp1\u2010Cre<\/i> Transgene and the <i>Rosa<sup>Notch<\/sup><\/i> Allele"],"prefix":"10.1002","volume":"117","author":[{"given":"Stefano","family":"Zanotti","sequence":"first","affiliation":[{"name":"Departments of Orthopaedic Surgery and Medicine, and The UConn Musculoskeletal Institute UConn Health Farmington 06030 Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernesto","family":"Canalis","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery and Medicine, and The UConn Musculoskeletal Institute UConn Health Farmington 06030 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