ORIGINAL RESEARCH article
Front. Physiol.
Sec. Craniofacial Biology and Dental Research
Thiamet-G facilitates reparative dentin formation via modulating O-GlcNAcylation and inflammation
Provisionally accepted
Elina Pokharel1
Tae-Young Kim1,2
Bandana Rana1Je-Hee Jang1Jae-Hee Lee1Seo-Young An1Chang-Hyeon An1
Hitoshi Yamamoto3
Wern-joo Sohn4
Youngkyun Lee1
Jung-Hong Ha1Do-Yeon Kim1Jae-Kwang Jung1*
Jae-Young Kim1*- 1Kyungpook National University, Daegu, Republic of Korea
- 2Keimyung University, Dalseo-gu, Republic of Korea
- 3Tokyo Dental College, Tokyo, Japan
- 4Daegu Haany University, Gyeongsan-si, Republic of Korea
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Introduction: O-GlcNAcylation, a reversible post-translational modification is involved in various cellular processes, such as proliferation, differentiation, and inflammation modulation. Developmental study revealed that proper O-GlcNAcylation mediated by OGT is vital for tooth morphogenesis. However, the function of O-GlcNAcylation during reparative dentin formation is still unknown. To understand its therapeutic relevance in regenerative dentistry, we examined the potential of O-GlcNAcase inhibitor, Thiamet-G, in reparative dentin formation using both in vitro and in vivo approaches. Methods: Human dental pulp stem cells were cultivated to examine cell viability, alkaline phosphatase (ALP) activity, and mRNA expression of reparative dentin-related genes. Furthermore, the dental pulp of the upper first molar in 8-week-old male ICR mice was exposed, and Thiamet-G was locally delivered for in vivo studies. Histological and immunohistochemical alterations were analyzed after 3 and 5 days post-cavity preparation, and dentin-bridge formation was evaluated at 42 days using histology and micro-CT. Results: In vitro, Thiamet-G treatment facilitated proliferation, ALP activity, and upregulated expression of reparative dentin-related genes, including BMP2, BSP, DSPP, OCN, and RUNX2. In vivo, Thiamet-G treated specimens showed the altered localizations of NESTIN, NF-κB, MPO, OPN, RUNX2, TGF-β1, and TNF-α at 3 and 5 days post exposure, suggesting enhanced dentin regeneration and modulated inflammation. Particularly, at 42 days, Thiamet-G treated specimens exhibited enhanced dentin-bridge formation, confirmed by micro-CT imaging and histology.
Keywords: Inflammation, OGA, O-GlcNAcylation, Pulp cavity, Reparative dentine, Thiamet-G
Received: 04 Nov 2025; Accepted: 19 Dec 2025.
Copyright: © 2025 Pokharel, Kim, Rana, Jang, Lee, An, An, Yamamoto, Sohn, Lee, Ha, Kim, Jung and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jae-Kwang Jung
Jae-Young Kim
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.