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Potential function of TGF-β isoforms in maturation-stage ameloblasts.

Miu Okubo1, Risako Chiba2, Takeo Karakida2

  • 1Department of Periodontology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.

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Summary

Transforming growth factor-beta (TGF-β) isoforms regulate ameloblast function during tooth development. These growth factors influence gene expression, apoptosis, and amelogenin uptake in a specific manner.

Keywords:
AmeloblastApoptosisEnamelEndocytosisTransforming growth factor-beta

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Area of Science:

  • Cell biology
  • Developmental biology
  • Biochemistry

Background:

  • Amelogenesis, the process of tooth enamel formation, involves complex cellular signaling.
  • Transforming growth factor-beta (TGF-β) signaling is crucial for regulating cell behavior during development.
  • The specific roles of different TGF-β isoforms in maturation-stage ameloblasts remain incompletely understood.

Purpose of the Study:

  • To investigate the functional roles of TGF-β isoforms in maturation-stage ameloblasts during amelogenesis.
  • To elucidate the isoform-specific effects of TGF-β on ameloblast gene expression, apoptosis, and protein uptake.

Main Methods:

  • Utilized Mmp20 null and wild-type mice to study in vivo TGF-β activation.
  • Employed mHAT9d cells treated with TGF-β isoforms to assess cell proliferation (MTS assay), apoptosis (cleaved caspase-3 immunostaining), gene expression (RT-qPCR), and amelogenin uptake (fluorescence microscopy).

Main Results:

  • TGF-β1 and TGF-β3 were found in the developing enamel matrix and activated by MMP20.
  • All three TGF-β isoforms modulated the expression of genes involved in enamel structure and ion transport (KLK4, carbonic anhydrase II, amelotin, ODAM, FAM83H, ALP).
  • TGF-β isoforms induced apoptosis in mHAT9d cells, with TGF-β3 being most potent, and promoted amelogenin endocytosis.

Conclusions:

  • TGF-β isoforms are regulated in an isoform-specific manner during amelogenesis.
  • These isoforms play multifaceted roles in maturation-stage ameloblasts, including regulating gene expression, mineral ion transport, apoptosis, and endocytosis.