Macrophages mediate corticotomy-accelerated orthodontic tooth movement

Yan Wang,Wen Sun,Shuting Zhang,Bin Yan,Lizhe Xie,Siyu Wang,Linlin Zhu,Yali Chen,Zongyang Sun,Hanwen Zhang

doi:10.1038/s41598-018-34907-5

Abstract

Clinical evidence has suggested that surgical corticotomy of the alveolar bone can accelerate local orthodontic tooth movement (OTM), but the underlying cell and molecular mechanisms remain largely unclear. The present study examined the role of macrophages played in corticotomy-assisted OTM. Orthodontic nickel-titanium springs were applied to the left maxillary first molars of rats or mice to induce OTM with or without corticotomy. Corticotomy enhanced OTM distance by accelerating movement through induction of local osteoclastogenesis and macrophage infiltration during OTM. Further analysis showed that macrophages were polarized toward an M1-like phenotype immediately after corticotomy and then switched to an M2-like phenotype during OTM. The microenvironment of corticotomy induced macrophage infiltration and polarization through the production of TNF-α. More importantly, the amount of OTM induced by corticotomy was significantly decreased after mice were depleted of monocyte/macrophages by injection of liposome-encapsulated clodronate. Further experiments by incubating cultured macrophages with fresh tissue suspension obtained from post-corticotomy gingiva switched the cells to an M1 phenotype through activation of the nuclear factor-κB (NF-κB) signaling pathway, and to an M2 phenotype through activation of the JAK/STAT3 signaling pathway. Our results suggest that corticotomy induces macrophage polarization first by activating the NF-κB signaling pathway and later by activating the JAK/STAT3 signaling pathway, and that these processes contribute to OTM by triggering production of inflammatory cytokines and osteoclastogenesis.

Highlights

The average duration of a comprehensive orthodontic treatment is 20–36 months[1]
A recent study found that polarization of M1-like macrophages was critical for alveolar bone resorption on the compression side and subsequent onset of orthodontic tooth movement (OTM), and monocyte/macrophage depletion drastically reduced the amount of osteoclasts and the OTM distance[15]
The present work confirms that macrophages are actively involved in corticotomy-accelerated OTM

Summary

Introduction

The average duration of a comprehensive orthodontic treatment is 20–36 months[1]. As prolonged treatment increases the risk of periodontal disease and root resorption, especially in adult patients[2,3], orthodontic professionals are constantly seeking ways to accelerate orthodontic tooth movement (OTM)[4]. The main functions of macrophages are twofold: inflammation and regeneration, respectively, by M1 and M2-polarized subtype macrophages[9] Both inflammatory and regenerative events have been found to be essential for wound healing in bone[11] as well as mechanically-induced OTM12. A recent study found that polarization of M1-like macrophages was critical for alveolar bone resorption on the compression side and subsequent onset of OTM, and monocyte/macrophage depletion drastically reduced the amount of osteoclasts and the OTM distance[15]. These findings strongly suggest that corticotomy-accelerated OTM is mediated by local monocytes/macrophages. We asked two specific questions: whether corticotomy alters the microenvironment of macrophages and affects their polarization and infiltration, and what molecular pathways are involved in these changes

Methods

Results

Conclusion