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The effects of testosterone on craniosynostotic calvarial cells: a test of the gene/environmental model of craniofacial anomalies
Author(s) -
Cray JJ,
Durham EL,
Smalley MA,
Finegold DN,
Siegel MI,
Losee JE,
Mooney MP,
Cooper GM
Publication year - 2011
Publication title -
orthodontics and craniofacial research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 55
eISSN - 1601-6343
pISSN - 1601-6335
DOI - 10.1111/j.1601-6343.2011.01520.x
Subject(s) - craniofacial , calvaria , testosterone (patch) , gene , biology , medicine , endocrinology , genetics , in vitro
To cite this article:
Cray JJ Jr, Durham EL, Smalley MA, Finegold DN, Siegel MI, Losee JE, Mooney MP, Cooper GM:
The effects of testosterone on craniosynostotic calvarial cells: a test of the gene/environmental model of craniofacial anomalies
Orthod Craniofac Res 2011; 14 :149–155 Structured Abstract Authors – Cray JJ Jr, Durham EL, Smalley MA, Finegold DN, Siegel MI, Losee JE, Mooney MP, Cooper GM Introduction – The gene–environmental interaction model for craniofacial development proposes that if a genetic predisposition for an anomaly is coupled with an environmental factor that can exacerbate this predisposition, more severe phenotypes will result. Here, we utilize cells derived from our non‐syndromic rabbit model of craniosynostosis to test the hypothesis that an insult, testosterone (TP) administration (exogenous source) will alter the osteogenic activity of these cells. Design – Calvarial cells from wild‐type (WT) (N = 13) or craniosynostotic (CS) rabbits (N = 11) were stimulated with TP, an androgen receptor blocker, flutamide, and combined treatments. Proliferation and differentiation assays were conducted after 7 days. anova and t ‐tests were used to determine differences in stimulation and cell type. Results – The CS cells had significantly greater proliferation after TP administration compared to WT. There were no appreciable changes in differentiation after TP stimulation. Flutamide administration or combined TP and flutamide administration decreased both proliferation and differentiation for both cell types similarly. Conclusions – Testosterone exposure caused an increase in cell proliferation for CS osteoblast cells. However, a therapy targeted to mitigate this response (flutamide therapy) similarly affected CS and WT cells, suggesting that the administration of flutamide or TP in the presence of flutamide decreases osteogenesis of these cells. Thus, although our data support a mechanism of gene–environmental interaction, these results would not support a therapeutic intervention based on this interaction.