M1-like Macrophage Polarization Promotes Orthodontic Tooth Movement

Abstract

Macrophages play a crucial role in inflammatory-mediated bone loss. Orthodontic tooth movement (OTM) is associated with inflammatory bone remodeling. However, whether and how macrophages contribute to mechanical force-induced OTM remains unknown. In this study, we hypothesized that polarization of M1-like macrophages may contribute to the OTM. Orthodontic nickel-titanium springs were applied to the upper first molars of rats or mice to induce OTM. The distance of OTM gradually increased after mechanical force was applied to the rats for 5 and 10 d. M1-like macrophage polarization and expression of M1 cytokine tumor necrosis factor (TNF)-α also increased after force application. More importantly, monocyte/macrophage depletion in mice by injection of clodronate liposomes decreased the distance of OTM and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68(+) macrophages, accompanied by reduced expressions of M1 markers TNF-α and inducible nitric oxide synthase (iNOS), whereas systemic transfusion of M1 macrophages in mice increased them. Further experiments showed that injection of recombinant TNF-α increased the distance of OTM and the number of TRAP-positive osteoclasts and CD68(+) macrophages, as well as upregulated the expression of TNF-α and iNOS. Blockage of TNF-α by etanercept injection reduced the distance of OTM and the number of TRAP-positive osteoclasts and CD68(+) macrophages, as well as decreased the levels of TNF-α and iNOS. These data suggest that M1-like macrophage polarization promotes alveolar bone resorption and consequent OTM after mechanical force application.

NLRP3 inflammasome mediates M1 macrophage polarization and IL‐1β production in inflammatory root resorption

“…In vitro, force‐pre‐treated hPDLCs promoted M1 macrophage polarization in the co‐culture system and increased IL‐1β production in M1 macrophages. He et al found that the number of M1 macrophages was increased around the roots of the rat force‐induced inflammatory RR model and that mechanical force induced the polarization of macrophages to the M1 subtype (He, Kou, Luo, et al, ; He, Kou, Yang, et al, ), which is consistent with our results.…”

“…M1 macrophages mainly secrete IL‐1β, IL‐12, IL‐18, tumour necrosis factor‐α (TNF‐α), and other inflammatory cytokines, leading to inflammation (Chavez‐Galan, Olleros, Vesin, & Garcia, ). In 2015, He et al found that when the number of M1 subtype macrophages or the proportion of M1/M2 macrophages increased in periodontal tissues, RR in rats with orthodontic tooth movement was elevated (He, Kou, Luo, et al, ; He, Kou, Yang, et al, ). Therefore, IL‐1β and M1 macrophages might play critical roles in the development of RR.…”

“…Previous studies have shown that the interaction of fibroblasts with the immune cells, such as macrophages, was involved in the process of inflammation (El Kasmi et al, ; Smith, Smith, Blieden, & Phipps, ). He reported that after orthodontic force application, periodontal ligament cells (PDLCs) could secrete cytokines, such as IFN‐γ, to stimulate M1 macrophage transformation (He, Kou, Yang, et al, ).…”

MicroRNA‐21 promotes orthodontic tooth movement by modulating the RANKL/OPG balance in T cells

“…The immune system has a pivotal effect on bone resorption, giving rise to the osteoimmunology concept. T cells contribute to OTM via Th1‐related cytokines (Yan et al, ), and the innate immune response is also necessary for OTM (He, Kou, Luo, et al, ; He, Kou, Yang, et al, ). In addition to the dominant involvement of RANKL in bone resorption, several studies have emphasized links between RANKL and immune cells.…”

Mechanosensing by Gli1+ cells contributes to the orthodontic force‐induced bone remodelling

“…The sagittal and horizontal images were acquired through three‐dimensional reconstructions. OTM distance was measured as previously described 17 …”