GSK3beta inhibitor-induced dental mesenchymal stem cells regulate ameloblast differentiation

Aya Yamada; Keigo Yoshizaki; Kan Saito; Masaki Ishikawa; Yuta Chiba; Seira Hoshikawa; Mitsuki Chiba; Ryoko Hino; Yuriko Maruya; Hiroshi Sato; Keiji Masuda; Haruyoshi Yamaza; Takashi Nakamura; Tsutomu Iwamoto; Satoshi Fukumoto

doi:10.1016/j.job.2022.10.002

GSK3beta inhibitor-induced dental mesenchymal stem cells regulate ameloblast differentiation

J Oral Biosci. 2022 Dec;64(4):400-409. doi: 10.1016/j.job.2022.10.002. Epub 2022 Oct 18.

Authors

Affiliations

¹ Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
² Section of Orthodontics and Dentofacial Orthopedics, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
³ Perelman School of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴ Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
⁵ Division of Molecular Pharmacology and Cell Biophysics, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
⁶ Department of Pediatric Dentistry/ Special Needs Dentistry, Division of Oral Health Science, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.
⁷ Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan; Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan. Electronic address: fukumoto@dent.kyushu-u.ac.jp.

PMID: 36270608
DOI: 10.1016/j.job.2022.10.002

Abstract

Objectives: Epithelial-mesenchymal interactions are extremely important in tooth development and essential for ameloblast differentiation, especially during tooth formation. We aimed to identify the type of mesenchymal cells important in ameloblast differentiation.

Methods: We used two types of cell culture systems with chambers and found that a subset of debtal mesenchimal cells is important for the differentiatiuon of dental spithelial cells into ameloblasts. Further, we induced dental pulp stem cell-like cells from dental pulp stem cells using the small molecule compound BIO ( a GSK-3 inhibitor IX) to clarify the mechanism involved in ameloblast differentiation induced by dental pulp stem cells.

Results: The BIO-induced dental pulp cells promoted the expression of mesenchymal stem cell markers Oct3/4 and Bcrp1. Furthermore, we used artificial dental pulp stem cells induced by BIO to identify the molecules expressed in dental pulp stem cells required for ameloblast differentiation. Panx3 expression was induced in the dental pulp stem cell through interaction with the dental epithelial cells. In addition, ATP release from cells increased in Panx3-expressing cells. We also confirmed that ATP stimulation is accepted in dental epithelial cells.

Conclusions: These results showed that the Panx3 expressed in dental pulp stem cells is important for ameloblast differentiation and that ATP release by Panx3 may play a role in epithelial-mesenchymal interaction.

Keywords: Ameloblast; Ameloblastin; Epithelial–mesenchymal interaction; GSK3beta inhibitor; pannexin3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism
Ameloblasts* / metabolism
Glycogen Synthase Kinase 3 / metabolism
Glycogen Synthase Kinase 3 beta / metabolism
Mesenchymal Stem Cells*

Substances

Glycogen Synthase Kinase 3 beta
Glycogen Synthase Kinase 3
Adenosine Triphosphate