Ezh2 knockout in mesenchymal cells causes enamel hyper-mineralization
Document Type
Article
Publication Date
8-27-2021
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.
Identifier
85108012159 (Scopus)
Publication Title
Biochemical and Biophysical Research Communications
External Full Text Location
https://doi.org/10.1016/j.bbrc.2021.06.003
e-ISSN
10902104
ISSN
0006291X
PubMed ID
34144503
First Page
72
Last Page
78
Volume
567
Grant
S10OD010751-01A1
Fund Ref
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Recommended Citation
Kobayashi, Yoshifumi; Quispe-Salcedo, Angela; Bodas, Sanika; Matsumura, Satoko; Li, Erhao; Johnson, Richard; Choudhury, Marwa; Fine, Daniel H.; Nadimpalli, Siva; Duncan, Henry F.; Dudakovic, Amel; van Wijnen, Andre J.; and Shimizu, Emi, "Ezh2 knockout in mesenchymal cells causes enamel hyper-mineralization" (2021). Faculty Publications. 3866.
https://digitalcommons.njit.edu/fac_pubs/3866
