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Time-Series Transcriptomics Identifies Xanthine Dehydrogenase in Injured Neurons Correlated With Orthodontic Pain
Xiaoqi Zhang1, Lu Xing1, Xiaoqian Zhang2
1State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Orthodontics & Craniofacial Research
|September 26, 2025
Summary
Orthodontic tooth movement pain involves injured trigeminal ganglion neurons. Xanthine dehydrogenase (Xdh) upregulation in these neurons intensifies pain, suggesting Xdh as a therapeutic target for orthodontic pain relief.
Area of Science:
- Neuroscience
- Molecular Biology
- Biomedical Engineering
Background:
- Orthodontic tooth movement (OTM) causes significant pain, a major clinical issue.
- The molecular and cellular basis of OTM pain is not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms of OTM pain.
- To identify potential therapeutic targets for OTM pain.
Main Methods:
- Established a mouse OTM model with micro-CT and histology.
- Conducted pain assessments using Mouse Grimace Scale and bite force.
- Performed bulk RNA sequencing on trigeminal ganglion (TG) tissues and integrated with single-cell RNA-seq data.
- Confirmed key gene expression using qPCR and immunofluorescence.
- Developed the OTMPTGTA web platform for data exploration.
Main Results:
- OTM induced significant tooth movement and peak pain at Day 3.
- Transcriptomic analysis revealed an Atf3+ neuronal population in TG with upregulated xanthine dehydrogenase (Xdh) during peak pain.
- Xdh expression and pain scores decreased by Day 14.
- qPCR and immunofluorescence confirmed coexpression of Atf3 and Xdh in injured TG neurons at Day 3, implicating Xdh in nociceptive signaling.
Conclusions:
- Xanthine dehydrogenase (Xdh) is highly expressed in injured neurons during OTM pain, likely exacerbating nociceptive signals.
- Xdh presents a promising therapeutic target for managing orthodontic pain while allowing for effective tooth movement.
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