# Biological Interplay between Orthodontic Forces and Apical Papilla-derived Stem Cells: A Review on Mechanisms and Implications: -

## TL;DR

This review explores how orthodontic forces and stem cells from the apical papilla interact, influencing dental cell behavior and potential therapies.

## Contribution

The paper provides new insights into how various factors modulate dental stem cell differentiation for improved orthodontic and endodontic treatments.

## Key findings

- Advanced glycation end-products inhibit osteogenesis via KDM6B and Wnt/β-catenin suppression.
- Nano-dentine enhances osteogenic gene expression compared to MTA and Biodentine.
- Low-energy blue LED stimulates osteogenic differentiation despite reduced proliferation.

## Abstract

Orthodontics is not limited to the movement of teeth, but has also expanded
to the cellular and molecular realms. In this study, it was aimed to review
mechanisms and implications of biological interplay between orthodontic
forces and apical papilla-derived stem cells.

This narrative and semi-systematic review investigates the biological
interactions between orthodontic forces and stem cells derived from the
apical papilla (SCAPs). A comprehensive literature search was conducted in
PubMed, Web of Science, and Google Scholar using specific keywords and MeSH
terms from 2015 to 2025. Studies in English and Persian were included if
they focused on the effects of orthodontic forces on SCAPs’ function,
differentiation, or signaling pathways. Key biological mechanisms and
molecular responses were extracted and analyzed.

Between 2015 and 2025, 10 studies were included, primarily investigating
human dental stem cells (SCAPs, DPCs, PDLSCs, SHEDs) and rat models.
Findings showed that advanced glycation end-products inhibit osteogenesis
via KDM6B and Wnt/β-catenin suppression, whereas Ape1 inhibition promotes
odontogenic differentiation through the same pathway. Nano-dentine enhanced
osteogenic gene expression compared to MTA and Biodentine, and low-energy
blue LED stimulated osteogenic differentiation despite reduced
proliferation. TGF-β1 had dose-dependent effects on SCAP proliferation and
differentiation, while FTO/SMOC2 regulated odontoblastic differentiation
under inflammatory conditions. Mechanical forces reduced SHED proliferation
without affecting apoptosis, and pathogenic bacteria like F. nucleatum and
E. faecalis impaired SCAP proliferation, viability, and osteogenic gene
expression, indicating that molecular, material, mechanical, and microbial
factors critically modulate dental stem cell differentiation.

Current evidence shows that various physical, chemical, microbial, and
molecular factors influence dental stem cell behavior. Understanding these
mechanisms can support the development of personalized therapies, enhancing
outcomes in endodontic and orthodontic treatments, particularly under
pathological conditions like diabetes and chronic inflammation.