Evidence map›Paper›PMID 27453922›Full record

ArticleBone reports2016

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 and 2 more

Open access · goldAbstract read
In one paragraph

Article in Bone reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.5field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 34 citations in OpenAlex.

  1. eLife · 2025
    Article
  2. Article
  3. bioRxiv : the preprint server for biology · 2025
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  9. Technologies, strategies, and cautions when deconvoluting genome-wide association signals: FTO in focus.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2023
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Regulation and Role of Transcription Factors in Osteogenesis.International journal of molecular sciences · 2021
    Review
  16. Irx3 and Irx5 in Ins2-CreNature metabolism · 2021
    Article
  17. Article
  18. Frontiers in neuroscience · 2021
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 5 countries.

Corey J CainDepartment of Medicine, Division of Endocrinology and Metabolism, Institute for Human Genetics, Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA 94143-0794, USA.
Nathalie GaboritInserm, UMR 1087, l'institut du thorax, Nantes, France; CNRS, UMR 6291, Nantes, France; Université de Nantes, France.
Wint LwinDepartment of Medicine, Division of Endocrinology and Metabolism, Institute for Human Genetics, Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA 94143-0794, USA.
Emilie BarruetDepartment of Medicine, Division of Endocrinology and Metabolism, Institute for Human Genetics, Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA 94143-0794, USA.
Samantha HoDepartment of Medicine, Division of Endocrinology and Metabolism, Institute for Human Genetics, Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA 94143-0794, USA.
Carine BonnardHuman Embryology and Genetics Laboratory, Institute of Medical Biology, ASTAR, Singapore 138648, Singapore.
Hanan HamamyDepartment of Genetic Medicine and Development, Geneva University, Geneva 1211, Switzerland.
Mohammad ShboulHuman Embryology and Genetics Laboratory, Institute of Medical Biology, ASTAR, Singapore 138648, Singapore.
Bruno ReversadeHuman Embryology and Genetics Laboratory, Institute of Medical Biology, ASTAR, Singapore 138648, Singapore.
Hülya KayseriliMedical Genetics Department, Koc University School of Medicine, Rumelifeneri Yolu, Sarıyer, Istanbul 34450, Turkey; Medical Genetics Department, Istanbul Medical Faculty, Istanbul University Topkapi, Fatih, 34093 lstanbul, Turkey.
Benoit G BruneauGladstone Institute for Cardiovascular Disease, San Francisco, CA 94158, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
Edward C HsiaoDepartment of Medicine, Division of Endocrinology and Metabolism, Institute for Human Genetics, Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA 94143-0794, USA.
University of California, San Francisco · USAgency for Science, Technology and Research · SGCentre National de la Recherche Scientifique · FRGladstone Institutes · USKoç University · TRUniversity of Geneva · CH

Funding

DIABETES, ENDOCRINOLOGY &METABOLISM TRAINING PROGRAMT32DK007418 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EDWARD C HSIAO · 1986 to 2026
$14.3M
Training Program in Pediatric EndocrinologyT32DK007161 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian J Feldman, STEPHEN E GITELMAN · 1986 to 2026
$6.2M
POSTDOCTORAL TRAINING IN MEDICAL GENETICST32GM007085 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SLAVOTINEK, ANNE M. · 1985 to 2013
$1.9M
Iroquois Homeobox Transcription Factors in Heart Development and PhysiologyR01HL093414 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI BRUNEAU, BENOIT GAETAN · 2009 to 2010
$955k
Regulation of Bone Formation by G-protein SignalingK08AR056299 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HSIAO, EDWARD C · 2009 to 2013
$640k
NHLBI NIH HHS R01 HL093414NIAMS NIH HHS K08 AR056299NIDDK NIH HHS T32 DK007161NIDDK NIH HHS T32 DK007418NIGMS NIH HHS T32 GM007085
6 · The paper itself

Abstract

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.

Indexed as

Osteoblast mineralizationOsteoclast/osteoblast biologyOsteoporosis

Identifiers

PMID27453922
PMCPMC4926823
OpenAlexW2336889525

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.