Macrophage ATF6 accelerates corticotomy-assisted orthodontic tooth movement through promoting Tnfα transcription.
10.1038/s41368-025-00359-7
- Author:
Zhichun JIN
1
;
Hao XU
1
;
Weiye ZHAO
1
;
Kejia ZHANG
1
;
Shengnan WU
1
;
Chuanjun SHU
2
;
Linlin ZHU
1
;
Yan WANG
1
;
Lin WANG
3
;
Hanwen ZHANG
4
;
Bin YAN
5
Author Information
1. Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
2. Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China.
3. Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China. lw603@njmu.edu.cn.
4. School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China. hanwenzhang@njmu.edu.cn.
5. Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China. byan@njmu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Animals;
Mice;
Macrophages/metabolism*;
Tumor Necrosis Factor-alpha/genetics*;
Tooth Movement Techniques/methods*;
Activating Transcription Factor 6/metabolism*;
Bone Remodeling;
Flow Cytometry;
Blotting, Western
- From:
International Journal of Oral Science
2025;17(1):28-28
- CountryChina
- Language:English
-
Abstract:
Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon (RAP). Despite its therapeutic effects, the surgical risk and unclear mechanism hamper the clinical application. Numerous evidences support macrophages as the key immune cells during bone remodeling. Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1CreERT2; R26GFP lineage tracing system. Fluorescence staining, flow cytometry analysis, and western blot determined the significantly enhanced expression of binding immunoglobulin protein (BiP) and emphasized the activation of sensor activating transcription factor 6 (ATF6) in macrophages. Then, we verified that macrophage specific ATF6 deletion (ATF6f/f; CX3CR1CreERT2 mice) decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy. In contrast, macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement. In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6. At the mechanism level, RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfα promotor and augmenting its transcription. Additionally, molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element (ERSE). Taken together, ATF6 may aggravate orthodontic bone remodeling by promoting Tnfα transcription in macrophages, suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.
