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Neutrophils Orchestrate Osteoclastogenesis in Orthodontic Tooth Movement

ABSTRACT: To elucidate the biological mechanisms of alveolar bone remodeling during orthodontic tooth movement (OTM), we performed single-cell RNA sequencing (scRNA-seq) on periodontal ligament (PDL) tissues from a mouse OTM model. We identified 11 distinct cell clusters and revealed that neutrophils are a primary source of pro-inflammatory cytokines such as TNF, IL-1β, and OSM. Our analysis identified a specific “Inflammatory-Neu” subset that expands during OTM and coordinates macrophage recruitment. This study demonstrates that neutrophils act as indispensable upstream regulators that drive osteoclastogenesis during mechanical loading.

ORGANISM(S): Mus musculus

PROVIDER: GSE324651 | GEO | 2026/07/10

REPOSITORIES: GEO

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Macrophage ATF6 Accelerates Orthodontic Tooth Movement through Promoting Tnfα Transcription

Project description:Corticotomy is a clinical procedure targeting alveolar bone to activate regional acceleratory phenomenon (RAP) and promote orthodontic tooth movement (OTM). Corticotomy involves the orchestration of inflammation by macrophages, but the underlying mechanism remains unclear. Here, we identify endoplasmic reticulum (ER) stress sensor activating transcription factor 6 (ATF6) as a critical player modulating pro- and anti-inflammatory macrophage polarization. We show that macrophage-specific ATF6 deletion blocks corticotomy-induced OTM acceleration, while macrophage ATF6 overexpression exaggerates the acceleration effect. Furthermore, the proportion of pro-inflammatory macrophages is positively correlated with ATF6 expression in vitro and in vivo. By RNA-seq and CUT&Tag, we demonstrate that ATF6 interacts with Tnfα promotor and augments its transcription, thereby mediating the effect of TNF signaling pathway in pro-inflammatory macrophage polarization. In summary, ATF6 may aggravate alveolar bone remodeling during corticotomy by promoting Tnfα transcription in macrophages, suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerating orthodontics.

2025-04-09 | GSE245975 | GEO

Macrophage ATF6 Accelerates Orthodontic Tooth Movement through Promoting Tnfα Transcription

2025-04-09 | GSE246048 | GEO

Importin-7 Promotes Tension-Induced Osteogenesis by Regulating RUNX2 Nuclear Translocation during Orthodontic Tooth Movement

Project description:Orthodontic tooth movement (OTM) is primarily driven by alveolar bone remodeling, wherein tension-induced osteogenesis plays a central role. Importin7 (IPO7) has been identified as a highly mechanoresponsive nuclear transport receptor (NTR). However, its role in regulating tension-induced osteogenesis during OTM and its underlying mechanism remains elusive. In the present study, cyclic tensile strain and a rat OTM model were used to investigate the role of IPO7. The results revealed that IPO7 was significantly expressed both in vitro and in vivo following exposure to mechanical stretch. Moreover, IPO7 knockdown inhibited tension-induced osteogenesis in BMSCs. Upon mechanical force stimulation, IPO7 translocated from the cytoplasm to the nucleus. Furthermore, immunoprecipitation (IP) coupled with mass spectrometry (MS) was performed and demonstrated that RUNX2 was one of the IPO7-interacting proteins related to osteogenesis. Although RUNX2 has been established to translocate to the nucleus to facilitate osteogenesis, whether it is IPO7 that regulate RUNX2 nuclear input during tension-induced osteogenesis remains to be determined. Then, the interaction between IPO7 and RUNX2 was further validated via co-immunoprecipitation (co-IP) and colocalization assays in BMSCs using immunofluorescence. Taken together, this study demonstrates that IPO7 promotes tension-induced osteogenesis by regulating the nucleoplasmic localization of RUNX2. Thus, targeting IPO7 may represent a prospective therapeutic strategy for enhancing alveolar bone remodeling and the efficacy of orthodontic treatment.

2025-10-06 | PXD061760 | Pride

Gene expression profile altered by orthodontic tooth movement during healing of surgical alveolar defect

Project description:An OTM-related healing model was established where a maxillary second premolar was protracted into the critical-sized defect for 6 weeks (Group DT6). As controls, natural healing models without OTM were set at 2 weeks (Group D2) and at 6 weeks (Group D6) after surgery. Total RNAs were extracted from dissected regenerated tissues and additionally from sound alveolar bone as a baseline (Group C). mRNA profiling was performed using microarray analysis.

2017-08-01 | GSE85459 | GEO

Identification of candidate immunity biomarkers associated with age-related variations in osteoclast activity following orthodontic tooth movement

Project description:This study provides a comprehensive examination of the influence of age on osteoclast activity during orthodontic tooth movement, analyzed through the lens of osteoimmunology, identifying key immune molecules and cells involved in the regulation.We identified key molecules that play an important role in orthodontic bone reconstruction by analyzing the differences in immune inflammatory differential gene expression across different age groups. These molecules, which facilitate macrophage migration to the local site and their differentiation into osteoclasts, as well as directly enhance osteoclast differentiation and function, are differentially expressed in young groups, but not in adult groups.

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single cell RNA sequencing (scRNA-seq) of mouse first molar and adjacent alveolar bone tissues with and without orthodontic loading

Project description:Single-cell RNA sequencing (scRNA-seq) was performed on mouse first molar and adjacent alveolar bone tissues (within 1 mm, buccal and palatal sides). Two groups were analyzed: non-loaded control and orthodontic tooth movement (OTM) after 1 day. The study aims to reveal early cellular and transcriptional changes induced by orthodontic force.

2026-02-09 | GSE309282 | GEO

Effect of corticision on orthodontic tooth movement in a rat model as assessed by RNA sequencing

Project description:Corticision is a common technique to accelerate orthodontic tooth movement; however, not much is known about the underlying mechanisms. In this study, we investigated the mechanism of alveolar tissue remodeling after corticision in a rat model of tooth movement (TM) by analyzing the differential transcriptome

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Transcriptional Expression in Human Periodontal Ligament Cells Subjected to Orthodontic Force: An RNA-Sequencing Study

Project description:Purpose : This study was performed to investigate the changes in gene expression in periodontal ligament (PDL) cells following mechanical stimulus through RNA sequencing. Method : Premolars extracted for orthodontic treatment were used. To stimulate the PDL cells, an orthodontic force of 100× g was applied to the premolar (experimental group; n = 11), whereas the tooth on the other side was left untreated (control group; n = 11). After the PDL cells were isolated from the extracted teeth, gene set enrichment analysis (GSEA), differentially expressed gene (DEG) analysis, and real-time PCR were performed to compare the two groups. Result : GSEA demonstrated that gene sets related to the cell cycle pathway were upregulated in PDL. Thirteen upregulated and twenty downregulated genes were found through DEG analysis. Real-time PCR results confirmed that five upregulated genes (CC2D1B, CPNE3, OPHN1, TANGO2, and UAP-1) and six downregulated genes (MYOM2, PPM1F, PCDP1, ATP2A1, GPR171, and RP1-34H18.1-1) were consistent with RNA sequencing results. Conclusion : Two upregulated genes, CPNE3 and OPHN1, and one downregulated gene, PPM1F, play an important role in PDL regeneration in humans when orthodontic force is applied.

2021-02-03 | GSE165988 | GEO

Bone morphogenetic protein 4 in human saliva during orthodontic therapy

Project description:In orthodontic therapy periodontal tissue responds to mechanical stimuli by bone remodeling mediated by specific molecules involved in periodontal regeneration and homeostasis. The resulting changes are reflected in the salivary proteome that is emerging as a valuable diagnostic tool. We analyzed the changes of saliva proteome during orthodontic tooth movement in 12 healthy male patients, presented with malocclusion treated by placement of fixed orthodontic appliance. Six patients with identical dental pathology, but no orthodontic therapy were used as control samples. Saliva was collected a day before, immediately after, and 2, 7 and 30 days after the placement of the fixed orthodontic appliance and analyzed by LC-MS. Total of 198 proteins were identified and classified on the basis of their functional characteristics. Proteins involved in bone remodeling, inflammation and healing were detected mostly 30 days after placement of the fixed orthodontic appliance. At this time point, Bone morphogenetic protein 4 emerged as a central player in the ongoing dental bone remodeling. Besides BMP4, BMP antagonists: BMP Binding Endothelial Regulator (BMPER), Insulin-like growth factor-binding protein 3 (IGFBP3), Cytoskeleton-associated protein 4 (CKAP4) and Fibroblast growth factor 5 (FGF5), were also identified. Presence of BMP4 in human saliva 30 days after the placement of orthodontic fixed appliance was confirmed by ELISA and concentration of BMP4 was 3.2 pg/ml. To date, there is no published data on the presence of BMP molecules or their antagonists in saliva or the gingival cervical fluid, regardless of different orthodontic treatments or disease. BMP4 is involved not only in orthodontic treatment, but also in processes involving tooth development and homeostasis. Therefore, a better understanding of its networks in bone remodeling during OTM is heralded.

2021-09-09 | PXD016481 | Pride

Mouse periodontal ligament tissue after orthodontic tooth movement

Project description:Mouse periodontal ligament tissue after orthodontic tooth movement for 14 days. Tissue was dissected by a laser microdissection microscope. Samples were analyzed separately at mesial (compression) and distal (tension) sides.

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