# The Osteoimmune Axis: Immune–Mechanical Crosstalk in Periodontal Bone Remodeling

## TL;DR

This paper introduces a new model explaining how mechanical forces and immune responses interact to influence bone remodeling during orthodontic tooth movement.

## Contribution

The Osteoimmune Axis Model unifies mechanical and immune mechanisms in periodontal remodeling, offering a novel framework for understanding variability in orthodontic outcomes.

## Key findings

- Compressive loading promotes M1 macrophage/Th17 pathways linked to bone resorption.
- Tensile strain supports M2 macrophages and Tregs, aiding tissue repair and bone formation.
- Stromal cells act as mechanosensors that modulate immune responses and cytokine gradients.

## Abstract

Background: Orthodontic tooth movement is traditionally explained through mechanical deformation of the periodontal ligament (PDL); however, increasing evidence indicates that immune mechanisms critically shape bone remodeling outcomes. Mechanical stimuli influence immune cell recruitment, cytokine release, and phenotypic polarization, but these components are rarely integrated into a unified framework. Conceptual framework: We propose the Osteoimmune Axis Model, a conceptual framework describing how mechanical loading may bias immune polarity and thereby gate periodontal remodeling. Compressive loading appears to favor an M1 macrophage/Th17-dominant program associated with pro-inflammatory cytokines and enhanced RANKL-mediated osteoclastogenesis. In contrast, tensile or physiological strains may favor M2 macrophages and regulatory T cells (Treg), supporting IL-10, TGF-β, angiogenesis, extracellular-matrix repair, and osteoblastic activity. Stromal cells are proposed to act as mechanosensors and immune amplifiers that shape cytokine gradients and feedback loops. Predictions: The model predicts that identical forces may produce divergent outcomes depending on immune baseline; load duration may be more destructive than peak magnitude; tensile strain may stabilize M2/Treg pathways; thin periodontal phenotypes may shift toward the catabolic pole at lower mechanical loads; ROS may amplify immune-mediated bone loss; and immunomodulation may raise the threshold for pathological remodeling. Conclusion: The Osteoimmune Axis integrates mechanobiology and immunology into a testable framework for explaining variability in orthodontic periodontal remodeling and for generating hypothesis-driven, immune-aware risk assessment.