Macrophage-MSCs Interplay in Orthodontic Bone Remodelling: Mechanics-Immunity-Stem Cell Axis

During orthodontic treatment, the balance of bone remodelling is dynamically regulated by macrophages and site-specific mesenchymal stem cells (MSCs) through the mechanics-immunity-stem cell axis. Polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype is driven by mechanical forces via mechanosensors such as the Piezo1 channel. Macrophage polarization is induced by MSCs through exosomes and cytokine feedback, establishing a positive feedback loop of 'inflammation resolution-bone regeneration'. Moreover, other immune cells such as neutrophils and T lymphocytes participate in modulating the microenvironment. The dynamic balance of bone remodelling is collectively maintained by crosstalk among key signalling pathways: Wnt/β-catenin for osteogenesis, RANKL/RANK for bone resorption, and PI3K-Akt for macrophage polarization. These insights offer actionable targets for developing adjunctive therapies to accelerate orthodontic bone remodelling and improve treatment efficiency. Therefore, understanding the crosstalk mechanism between macrophages and MSCs under mechanical force is of significant clinical importance for targeting this interaction axis to optimize orthodontic treatment and accelerate bone remodelling.