The potential role of chromodomain helicase DNA-binding protein 3 in defining the cervical width by regulating the early growth stage of the apical papilla during tooth development

Kento Shimamura; Toshiki Nojiri; Hisatomo Kondo; Yunosuke Ikeda; Rika Yasuhara; Hiroko Ida-Yonemochi; Keishi Otsu; Hidemitsu Harada; Kenji Mishima; Hayato Ohshima; Takuya Kobayashi; Tarou Irié

doi:10.1016/j.job.2024.100604

The potential role of chromodomain helicase DNA-binding protein 3 in defining the cervical width by regulating the early growth stage of the apical papilla during tooth development

J Oral Biosci. 2024 Dec 20:100604. doi: 10.1016/j.job.2024.100604. Online ahead of print.

Authors

Affiliations

¹ Division of Fixed Prosthodontics and Oral Implantology, Department of Prosthodontics, School of Dentistry, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan; Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.
² Division of Fixed Prosthodontics and Oral Implantology, Department of Prosthodontics, School of Dentistry, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
³ Department of Fixed Prosthodontics and Oral Implantology, Aichi Gakuin University, 2-11, Suemoridori, Chikusa-ku, Nagoya, 464-8651, Japan.
⁴ Division of Oral and Maxillofacial Surgery, Department of Oral and Maxillofacial Reconstructive Surgery, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan; Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.
⁵ Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
⁶ Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, 951-8514, Japan.
⁷ Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.
⁸ Division of Removable Prosthodontics and Oral Rehabilitation, Department of Prosthodontics, School of Dentistry, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
⁹ Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan. Electronic address: [email protected].

PMID: 39710094
DOI: 10.1016/j.job.2024.100604

Abstract

Objective: This study aimed to evaluate the role of the chromodomain helicase DNA-binding protein 3 (CHD3) in tooth morphogenesis in Chd3 knockout mice.

Methods: Chd3 knockout mice were generated using the CRISPR-Cas9 method. Mandibular first molars were extracted from the mice and their littermates and morphometrically analyzed. Subsequent histological and immunohistochemical analyses of teeth were performed at each developmental stage. Chd3 knockdown in mesenchymal cells from the dental papilla (mDP) and Hertwig's epithelial root sheath (HERS) was performed by Chd3 shRNA transduction or a control using an adenoviral vector. These effects were examined using cell proliferation assays and quantitative real-time polymerase chain reaction.

Results: Narrowing of tooth cervical width was observed in mandibular first molars of Chd3 knockout mice. On postnatal day (PN) 8, the cervical width was narrow before root formation in tooth germs. The number of Ki-67-positive cells decreased in the dental mesenchyme at PN1 and apical papilla at PN8. Chd3 promoted the proliferation of dental mesenchymal cells, but no significant changes were observed in HERS epithelial cells. Chd3 maintained sonic hedgehog (Shh) expression and inhibited that of bone morphogenetic protein (Bmp)4 in dental mesenchymal cells, maintaining Shh and Wnt3a expression and inhibited that of Bmp2 in HERS epithelial cells.

Conclusion: Chd3 may regulate tooth cervical width during the early growth stage of the apical papilla via Shh, Bmp, and Wnt signaling.

Keywords: Nucleosome Remodeling and Deacetylation complexes; apical papilla; chromodomain helicase DNA-binding protein 3; stem cell; tooth morphogenesis.