Emily L Durham1, R Nicole Howie1, Laurel Black1, Grace Bennfors1, Trish E Parsons2, Mohammed Elsalanty3,4, Jack C Yu4,5, Seth M Weinberg2, James J Cray6. 1. Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina. 2. Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 3. Departments of Oral Biology, Cellular Biology and Anatomy, Orthopaedic Surgery and Oral and Maxillofacial Surgery, Augusta University, Augusta, Georgia. 4. Institute for Regenerative and Reparative Medicine, Augusta University, Augusta, Georgia. 5. Department of Surgery, Division of Plastic Surgery, Augusta University, Augusta, Georgia. 6. Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina. crayj@musc.edu.
Abstract
BACKGROUND: Craniosynostosis, the premature fusion of one or more of the cranial sutures, is estimated to occur in 1:1800 to 2500 births. Genetic murine models of craniosynostosis exist, but often imperfectly model human patients. Case, cohort, and surveillance studies have identified excess thyroid hormone as an agent that can either cause or exacerbate human cases of craniosynostosis. METHODS: Here we investigate the influence of in utero and in vitro exogenous thyroid hormone exposure on a murine model of craniosynostosis, Twist 1 +/-. RESULTS: By 15 days post-natal, there was evidence of coronal suture fusion in the Twist 1 +/- model, regardless of exposure. With the exception of craniofacial width, there were no significant effects of exposure; however, the Twist 1 +/- phenotype was significantly different from the wild-type control. Twist 1 +/- cranial suture cells did not respond to thyroxine treatment as measured by proliferation, osteogenic differentiation, and gene expression of osteogenic markers. However, treatment of these cells did result in modulation of thyroid associated gene expression. CONCLUSION: Our findings suggest the phenotypic effects of the genetic mutation largely outweighed the effects of thyroxine exposure in the Twist 1 +/- model. These results highlight difficultly in experimentally modeling gene-environment interactions for craniosynostotic phenotypes. Birth Defects Research (Part A) 106:803-813, 2016.
BACKGROUND:Craniosynostosis, the premature fusion of one or more of the cranial sutures, is estimated to occur in 1:1800 to 2500 births. Genetic murine models of craniosynostosis exist, but often imperfectly model humanpatients. Case, cohort, and surveillance studies have identified excess thyroid hormone as an agent that can either cause or exacerbate human cases of craniosynostosis. METHODS: Here we investigate the influence of in utero and in vitro exogenous thyroid hormone exposure on a murine model of craniosynostosis, Twist 1 +/-. RESULTS: By 15 days post-natal, there was evidence of coronal suture fusion in the Twist 1 +/- model, regardless of exposure. With the exception of craniofacial width, there were no significant effects of exposure; however, the Twist 1 +/- phenotype was significantly different from the wild-type control. Twist 1 +/- cranial suture cells did not respond to thyroxine treatment as measured by proliferation, osteogenic differentiation, and gene expression of osteogenic markers. However, treatment of these cells did result in modulation of thyroid associated gene expression. CONCLUSION: Our findings suggest the phenotypic effects of the genetic mutation largely outweighed the effects of thyroxine exposure in the Twist 1 +/- model. These results highlight difficultly in experimentally modeling gene-environment interactions for craniosynostotic phenotypes. Birth Defects Research (Part A) 106:803-813, 2016.
Authors: Arturo Hernandez; M Elena Martinez; Steven Fiering; Valerie Anne Galton; Donald St Germain Journal: J Clin Invest Date: 2006-01-12 Impact factor: 14.808
Authors: Stephen R F Twigg; Chris Healy; Christian Babbs; Jacqueline A Sharpe; William G Wood; Paul T Sharpe; Gillian M Morriss-Kay; Andrew O M Wilkie Journal: Dev Dyn Date: 2009-02 Impact factor: 3.780
Authors: James J Cray; Seth M Weinberg; Trish E Parsons; R Nicole Howie; Mohammed Elsalanty; Jack C Yu Journal: Birth Defects Res A Clin Mol Teratol Date: 2014-10-12
Authors: R Nicole Howie; Samuel Herberg; Emily Durham; Zachary Grey; Grace Bennfors; Mohammed Elsalanty; Amanda C LaRue; William D Hill; James J Cray Journal: Int J Oral Sci Date: 2018-09-03 Impact factor: 6.344