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Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization

Cranial malformations are a significant cause of perinatal morbidity and mortality. Iroquois homeobox transcription factors (IRX) are expressed early in bone tissue formation and facilitate patterning and mineralization of the skeleton. Mice lacking Irx5 appear grossly normal, suggesting that redund...

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Autores principales: Cain, Corey J., Gaborit, Nathalie, Lwin, Wint, Barruet, Emilie, Ho, Samantha, Bonnard, Carine, Hamamy, Hanan, Shboul, Mohammad, Reversade, Bruno, Kayserili, Hülya, Bruneau, Benoit G., Hsiao, Edward C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926823/
https://www.ncbi.nlm.nih.gov/pubmed/27453922
http://dx.doi.org/10.1016/j.bonr.2016.02.005
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author Cain, Corey J.
Gaborit, Nathalie
Lwin, Wint
Barruet, Emilie
Ho, Samantha
Bonnard, Carine
Hamamy, Hanan
Shboul, Mohammad
Reversade, Bruno
Kayserili, Hülya
Bruneau, Benoit G.
Hsiao, Edward C.
author_facet Cain, Corey J.
Gaborit, Nathalie
Lwin, Wint
Barruet, Emilie
Ho, Samantha
Bonnard, Carine
Hamamy, Hanan
Shboul, Mohammad
Reversade, Bruno
Kayserili, Hülya
Bruneau, Benoit G.
Hsiao, Edward C.
author_sort Cain, Corey J.
collection PubMed
description Cranial malformations are a significant cause of perinatal morbidity and mortality. Iroquois homeobox transcription factors (IRX) are expressed early in bone tissue formation and facilitate patterning and mineralization of the skeleton. Mice lacking Irx5 appear grossly normal, suggesting that redundancy within the Iroquois family. However, global loss of both Irx3 and Irx5 in mice leads to significant skeletal malformations and embryonic lethality from cardiac defects. Here, we study the bone-specific functions of Irx3 and Irx5 using Osx-Cre to drive osteoblast lineage–specific deletion of Irx3 in Irx5(−/−) mice. Although we found that the Osx-Cre transgene alone could also affect craniofacial mineralization, newborn Irx3(flox/flox)/Irx5(−/−)/Osx-Cre(+) mice displayed additional mineralization defects in parietal, interparietal, and frontal bones with enlarged sutures and reduced calvarial expression of osteogenic genes. Newborn endochondral long bones were largely unaffected, but we observed marked reductions in 3–4-week old bone mineral content of Irx3(flox/flox)/Irx5(−/−)/Osx-Cre(+) mice. Our findings indicate that IRX3 and IRX5 can work together to regulate mineralization of specific cranial bones. Our results also provide insight into the causes of the skeletal changes and mineralization defects seen in Hamamy syndrome patients carrying mutations in IRX5.
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spelling pubmed-49268232017-03-21 Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization Cain, Corey J. Gaborit, Nathalie Lwin, Wint Barruet, Emilie Ho, Samantha Bonnard, Carine Hamamy, Hanan Shboul, Mohammad Reversade, Bruno Kayserili, Hülya Bruneau, Benoit G. Hsiao, Edward C. Bone Rep Article Cranial malformations are a significant cause of perinatal morbidity and mortality. Iroquois homeobox transcription factors (IRX) are expressed early in bone tissue formation and facilitate patterning and mineralization of the skeleton. Mice lacking Irx5 appear grossly normal, suggesting that redundancy within the Iroquois family. However, global loss of both Irx3 and Irx5 in mice leads to significant skeletal malformations and embryonic lethality from cardiac defects. Here, we study the bone-specific functions of Irx3 and Irx5 using Osx-Cre to drive osteoblast lineage–specific deletion of Irx3 in Irx5(−/−) mice. Although we found that the Osx-Cre transgene alone could also affect craniofacial mineralization, newborn Irx3(flox/flox)/Irx5(−/−)/Osx-Cre(+) mice displayed additional mineralization defects in parietal, interparietal, and frontal bones with enlarged sutures and reduced calvarial expression of osteogenic genes. Newborn endochondral long bones were largely unaffected, but we observed marked reductions in 3–4-week old bone mineral content of Irx3(flox/flox)/Irx5(−/−)/Osx-Cre(+) mice. Our findings indicate that IRX3 and IRX5 can work together to regulate mineralization of specific cranial bones. Our results also provide insight into the causes of the skeletal changes and mineralization defects seen in Hamamy syndrome patients carrying mutations in IRX5. Elsevier 2016-04-13 /pmc/articles/PMC4926823/ /pubmed/27453922 http://dx.doi.org/10.1016/j.bonr.2016.02.005 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cain, Corey J.
Gaborit, Nathalie
Lwin, Wint
Barruet, Emilie
Ho, Samantha
Bonnard, Carine
Hamamy, Hanan
Shboul, Mohammad
Reversade, Bruno
Kayserili, Hülya
Bruneau, Benoit G.
Hsiao, Edward C.
Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization
title Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization
title_full Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization
title_fullStr Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization
title_full_unstemmed Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization
title_short Loss of Iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization
title_sort loss of iroquois homeobox transcription factors 3 and 5 in osteoblasts disrupts cranial mineralization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926823/
https://www.ncbi.nlm.nih.gov/pubmed/27453922
http://dx.doi.org/10.1016/j.bonr.2016.02.005
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