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

Corey J. Cain, Nathalie Gaborit, Wint Lwin, Emilie Barruet, Samantha Ho, Carine Bonnard, Hanan Hamamy, Mohammad Shboul, Bruno Reversade, Hülya Kayserili, Benoit G. Bruneau, Edward C. Hsiao

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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 Irx3flox/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 Irx3flox/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.
Original languageEnglish (US)
Pages (from-to)86-95
Number of pages10
JournalBone Reports
StatePublished - Dec 1 2016
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine


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