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Inositol-requiring enzyme 1 alpha is essential for dentinogenesis.

Qian Xu1,2, Tian Liang1,3, Jiahe Li1

  • 1Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX, United States.

Frontiers in Physiology
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Inositol-requiring enzyme 1 alpha (IRE1α) is crucial for odontoblast function and dentin formation. Loss of IRE1α function impairs dentinogenesis and worsens dental defects in mice with a dentinogenesis imperfecta-like phenotype.

Keywords:
dentin formationdentin sialophosphoprotein (DSPP)dentinogenesis imperfecta (DGI)inositol-requiring enzyme 1 alpha (IRE1α)odontoblastunfolded protein response (UPR)

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Developmental Biology

Background:

  • Inositol-requiring enzyme 1 alpha (IRE1α) is a key sensor of endoplasmic reticulum (ER) stress, vital for secretory cell maturation and implicated in human diseases.
  • Odontoblasts are critical for dentin formation, and their dysfunction leads to dental defects like dentinogenesis imperfecta (DGI).

Purpose of the Study:

  • To investigate the role of IRE1α in odontoblast development and dentin formation.
  • To analyze the impact of IRE1α deficiency on dentinogenesis in the context of a pathogenic dentin sialophosphoprotein (DSPP) variant.

Main Methods:

  • Utilized Western-blotting, stains-all staining, immunohistochemistry, and RT-PCR to assess protein secretion and IRE1α/XBP1 pathway activation in wild-type and mutant mice.
  • Generated genetically modified mice (2.3 Col1-Cre;Ern1fl/fl and compound mutants) to study IRE1α function in tooth development.
  • Analyzed structural and histological changes in mandibular molars using radiography, micro-CT, and histology.

Main Results:

  • Mutant P19L-DSPP protein accumulated within odontoblasts, indicating impaired secretion.
  • IRE1α and XBP1 pathway activation (increased p-IRE1α, total XBP1, spliced XBP1S) was observed in odontoblasts of DSPP mutant mice.
  • Loss of IRE1α function reduced dentin formation and exacerbated dental defects in DSPP mutant mice, while normalizing pulp chamber dentin thickness.

Conclusions:

  • IRE1α plays an essential role in odontoblast function and dentinogenesis.
  • The study reveals a context-dependent pathogenic role for IRE1α in dental tissue development and disease, highlighting the significance of ER stress pathways.