{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:28:31Z","timestamp":1787124511181,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1120989"],"award-info":[{"award-number":["APP1120989"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1042677"],"award-info":[{"award-number":["APP1042677"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Saethre\u2013Chotzen syndrome (SCS), associated with\n                      <jats:italic>TWIST\u20101<\/jats:italic>\n                      mutations, is characterized by premature fusion of cranial sutures.\n                      <jats:italic>TWIST\u20101<\/jats:italic>\n                      haploinsufficiency, leads to alterations in suture mesenchyme cellular gene expression patterns, resulting in aberrant osteogenesis and craniosynostosis. We analyzed the expression of the TWIST\u20101 target,\n                      <jats:italic>Tyrosine kinase receptor c\u2010ros\u2010oncogene 1<\/jats:italic>\n                      (\n                      <jats:italic>C\u2010ROS\u20101<\/jats:italic>\n                      ) in\n                      <jats:italic>TWIST\u20101<\/jats:italic>\n                      haploinsufficient calvarial cells derived from SCS patients and calvaria of\n                      <jats:italic>\n                        Twist\u20101\n                        <jats:sup>del\/+<\/jats:sup>\n                      <\/jats:italic>\n                      mutant mice and found it to be highly expressed when compared to\n                      <jats:italic>TWIST\u20101<\/jats:italic>\n                      wild\u2010type controls. Knock\u2010down of\n                      <jats:italic>C\u2010ROS\u20101<\/jats:italic>\n                      expression in\n                      <jats:italic>TWIST\u20101<\/jats:italic>\n                      haploinsufficient calvarial cells derived from SCS patients was associated with decreased capacity for osteogenic differentiation in vitro. Furthermore, treatment of human SCS calvarial cells with the tyrosine kinase chemical inhibitor, Crizotinib, resulted in reduced C\u2010ROS\u20101 activity and the osteogenic potential of human SCS calvarial cells with minor effects on cell viability or proliferation. Cultured human SCS calvarial cells treated with Crizotinib exhibited a dose\u2010dependent decrease in alkaline phosphatase activity and mineral deposition, with an associated decrease in expression levels of\n                      <jats:italic>Runt\u2010related transcription factor 2<\/jats:italic>\n                      and\n                      <jats:italic>OSTEOPONTIN<\/jats:italic>\n                      , with reduced PI3K\/Akt signalling in vitro. Furthermore, Crizotinib treatment resulted in reduced BMP\u20102 mediated bone formation potential of whole\n                      <jats:italic>\n                        Twist\u20101\n                        <jats:sup>del\/+<\/jats:sup>\n                      <\/jats:italic>\n                      mutant mouse calvaria organotypic cultures. Collectively, these results suggest that\n                      <jats:italic>C\u2010ROS\u20101<\/jats:italic>\n                      promotes osteogenic differentiation of\n                      <jats:italic>TWIST\u20101<\/jats:italic>\n                      haploinsufficient calvarial osteogenic progenitor cells. Furthermore, the aberrant osteogenic potential of these cells is inhibited by the reduction of C\u2010ROS\u20101. Therefore, targeting C\u2010ROS\u20101 with a pharmacological agent, such as Crizotinib, may serve as a novel therapeutic strategy to alleviate craniosynostosis associated with aberrant TWIST\u20101 function.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.26563","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:12:51Z","timestamp":1523923971000},"page":"7320-7332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Tyrosine kinase receptor c\u2010ros\u2010oncogene 1 inhibition alleviates aberrant bone formation of TWIST\u20101 haploinsufficient calvarial cells from Saethre\u2013Chotzen syndrome patients"],"prefix":"10.1002","volume":"233","author":[{"given":"Esther","family":"Camp","sequence":"first","affiliation":[{"name":"Mesenchymal Stem Cell Laboratory Adelaide Medical School Faculty of Health and Medical Sciences University of Adelaide Adelaide South Australia Australia"},{"name":"Cancer Theme South Australian Health and Medical Research Institute Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Cancer Theme South Australian Health and Medical Research Institute Adelaide South Australia Australia"},{"name":"Australian Craniofacial Unit Women's and Children's Hospital North Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C. W.","family":"Zannettino","sequence":"additional","affiliation":[{"name":"Cancer Theme South Australian Health and Medical Research Institute Adelaide South Australia Australia"},{"name":"Myeloma Research Laboratory Adelaide Medical School, Faculty of Health and Medical Sciences University of Adelaide Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta A.","family":"Glackin","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Neurosciences City of Hope National Medical Center and Beckman Research Institute Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6225-3084","authenticated-orcid":false,"given":"Stan","family":"Gronthos","sequence":"additional","affiliation":[{"name":"Mesenchymal Stem Cell Laboratory Adelaide Medical School Faculty of Health and Medical Sciences University of Adelaide Adelaide South Australia Australia"},{"name":"Cancer Theme South Australian Health and Medical Research Institute Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2008.07.006"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3981"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1597\/1545-1569_1997_034_0079_tcsisc_2.3.co_2"},{"issue":"4","key":"e_1_2_6_5_1","first-page":"228","article-title":"The hands in Saethre\u2013Chotzen syndrome","volume":"16","author":"Anderson P. 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