Ezh2 knockout in mesenchymal cells causes enamel hyper-mineralization

Yoshifumi Kobayashi, Angela Quispe-Salcedo, Sanika Bodas, Satoko Matsumura, Erhao Li, Richard Johnson, Marwa Choudhury, Daniel H. Fine, Siva Nadimpalli, Henry F. Duncan, Amel Dudakovic, Andre J. van Wijnen, Emi Shimizu

Research output: Contribution to journalArticlepeer-review

Abstract

Enhancer of zeste homolog 2 (EZH2) is the catalytic core of polycomb repressive complex 2 (PRC2), which primarily methylates lysine 27 on histone H3 (H2K27me3), generating transcriptionally suppressed heterochromatin. Since EZH2 suppresses expression of genes involved in dentin formation, we examined the role of EZH2 in tooth development. Intriguingly, microCT analysis of teeth from mice with conditional Ezh2 knockout in uncommitted mesenchymal cells showed hyper-mineralization of enamel, which is produced by the epithelial-lineage cells, ameloblasts. Scanning electron microscopy analysis and nano-indentation of the incisor enamel from knockout mice revealed smaller inter-rod spaces and higher hardness compared to wild type enamel, respectively. Interestingly, expression of the calcium channel subunit gene, Orai2, was decreased compared to its competitor, Orai1, both in knockout mouse incisors and the ex vivo culture of ameloblasts with the surrounding tissues under EZH2 inhibition. Moreover, histological analysis of incisor from knockout mice showed decreased ameloblastin and expedited KLK4 expression in the ameloblasts. These observations suggest that EZH2 depletion in dental mesenchymal cells reduces enamel matrix formation and increases enamel protease activity from ameloblasts, resulting in enamel hyper-mineralization. This study demonstrates the significant role of the suppressive H3K27me3 mark for heterochromatin on enamel formation.

Original languageEnglish (US)
Pages (from-to)72-78
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume567
DOIs
StatePublished - Aug 27 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Keywords

  • Ameloblast
  • Dental follicle cell
  • Enamel hyper-mineralization
  • EZH2
  • Histone methylation

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