Notch2 is involved in regulating apical tissue repair following severe intrusive luxation

Authors

  • Yuanpei He The Affiliated Stomatological Hospital, Southwest Medical University
  • Xuyan Gong School of Stomatology & Affiliated Stomatological Hospital, Tongji University
  • Cancan Ding The Affiliated Stomatological Hospital, Southwest Medical University
  • Yang Qiu The Affiliated Stomatological Hospital, Southwest Medical University
  • Guangwen Li The Affiliated Stomatological Hospital, Southwest Medical University
  • Shiting Li The Affiliated Stomatological Hospital, Southwest Medical University

DOI:

https://doi.org/10.1590/1678-7765-2025-0490

Keywords:

Intrusive luxation, Notch signaling pathway, Apical repair, Angiogenesis, Fibrillization

Abstract

This study aims to characterize apical repair dynamics in immature permanent teeth after severe intrusive luxation, and to explore Notch signaling pathway regulation in this process using a Sprague-Dawley rat model. Methodology  In this study, a modified tool was utilized to establish an intrusive luxation model in SD rats. Tissue repair was assessed via micro-computed tomography (Micro-CT) and hematoxylin-eosin (H&E) staining. Differential gene expression analysis of stem cells from the apical papilla (SCAPs) was performed using the publicly available GEO dataset. Immunohistochemical detection of Notch2 receptor expression in the apical region of injured teeth was subsequently conducted, guided by bioinformatics screening. Finally, the Notch signaling pathway was pharmacologically inhibited using DAPT (γ-secretase inhibitor), and its impact on post-injury prognosis was evaluated. Results  Histological analysis revealed prevalent pulp hypoplasia and apical tissue fibrosis after injury. Differential gene analysis suggested that the Notch signaling pathway, particularly Notch2, is involved in the regulation of angiogenesis-related pathways in SCAPs. Immunohistochemistry showed positive Notch2 expression in fibrotic apical regions. Notably, inhibition of Notch signaling significantly reduced aberrant fibrosis while enhancing vascular proliferation in the injury site. Conclusions  Severe intrusive luxation is primarily characterized by aberrant fibrous differentiation in the apical region. The Notch signaling pathway may negatively regulate angiogenesis in the damaged apical area, suggesting that targeted inhibition of this pathway could promote tissue repair following embedded dental injuries.

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Published

2026-03-02

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Section

Original Articles

How to Cite

He, Y., Gong, X., Ding, C., Qiu, Y., Li, G., & Li, S. (2026). Notch2 is involved in regulating apical tissue repair following severe intrusive luxation. Journal of Applied Oral Science, 34, e20250490. https://doi.org/10.1590/1678-7765-2025-0490