{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T07:57:15Z","timestamp":1725868635792},"reference-count":33,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2015,4,9]],"date-time":"2015-04-09T00:00:00Z","timestamp":1428537600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Alexion Pharmaceuticals Internationa","award":["sponsored research grant"],"award-info":[{"award-number":["sponsored research grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Orthod Craniofacial Res"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Structured Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and\/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue\u2010non\u2010specific alkaline phosphatase (<jats:styled-content style=\"fixed-case\">TNAP<\/jats:styled-content>) enzyme downstream of activating mutations in <jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Neonatal Crouzon (<jats:styled-content style=\"fixed-case\">FGFR<jats:sup>C<\/jats:sup><\/jats:styled-content><jats:sup>342Y\/+<\/jats:sup>) and wild\u2010type (<jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content><jats:sup>+\/+<\/jats:sup>) mice were injected with lentivirus to deliver a recombinant form of <jats:styled-content style=\"fixed-case\">TNAP<\/jats:styled-content>. Mice were sacrificed at 4\u00a0weeks postnatal. Serum was collected to test for alkaline phosphatase (<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>), phosphorus, and calcium levels. Craniofacial bone fusion and morphology were assessed by micro\u2010computed tomography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Injection with the <jats:styled-content style=\"fixed-case\">TNAP<\/jats:styled-content> lentivirus significantly increased serum <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> levels (increased serum <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphological analysis revealed craniofacial form differences for inferior surface (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.023) and cranial height (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.014) regions between <jats:styled-content style=\"fixed-case\">TNAP<\/jats:styled-content> lentivirus\u2010injected and vehicle\u2010injected Crouzon mice. With each unit increase in <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content> level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.068).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that <jats:styled-content style=\"fixed-case\">TNAP<\/jats:styled-content> deficiency may mediate <jats:styled-content style=\"fixed-case\">FGFR<\/jats:styled-content>2\u2010associated craniosynostosis. Future studies should incorporate injection of recombinant <jats:styled-content style=\"fixed-case\">TNAP<\/jats:styled-content> protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ocr.12080","type":"journal-article","created":{"date-parts":[[2015,4,11]],"date-time":"2015-04-11T00:45:13Z","timestamp":1428713113000},"page":"196-206","source":"Crossref","is-referenced-by-count":8,"title":["The effects of tissue\u2010non\u2010specific alkaline phosphatase gene therapy on craniosynostosis and craniofacial morphology in the FGFR2<sup>C342Y\/+<\/sup> mouse model of Crouzon craniosynostosis"],"prefix":"10.1111","volume":"18","author":[{"given":"E.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry School of Dentistry University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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E.","family":"Hatch","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry School of Dentistry University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,4,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32106"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-011-1615-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3182412a50"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukarGeneExpr.v20.i4.20"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405031101"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1597\/05-212"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-013-9701-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(03)00222-9"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.11.019"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21790"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1276205"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1999.14.6.883"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.279.4.R1365"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.142063399"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(85)90320-5"},{"key":"e_1_2_8_17_1","first-page":"2681","article-title":"The nucleoside triphosphate pyrophosphohydrolase isozyme PC\u20101 directly promotes cartilage calcification through chondrocyte apoptosis and increased calcium precipitation by mineralizing vesicles","volume":"8","author":"Johnson K","year":"2001","journal-title":"J Rheumatol"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.6.994"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.05.020"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.140021997"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.08.055"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.221689"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-008-0708-3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05387.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-40"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1106173"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008200500237203"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.081213"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.201"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.02.012"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(200002)217:2<137::AID-DVDY1>3.0.CO;2-N"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781420036176"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.071213"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.03.770"}],"container-title":["Orthodontics &amp; Craniofacial Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Focr.12080","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ocr.12080","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T07:46:59Z","timestamp":1694591219000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ocr.12080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4]]},"references-count":33,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2015,4]]}},"alternative-id":["10.1111\/ocr.12080"],"URL":"https:\/\/doi.org\/10.1111\/ocr.12080","archive":["Portico"],"relation":{},"ISSN":["1601-6335","1601-6343"],"issn-type":[{"value":"1601-6335","type":"print"},{"value":"1601-6343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4]]}}}