Time-Series Transcriptomics Identifies Xanthine Dehydrogenase in Injured Neurons Correlated With Orthodontic Pain.

IF 1.7 3区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE
Xiaoqi Zhang, Lu Xing, Xiaoqian Zhang, Waseem Ai-Gumaei, Qingxuan Wang, Minqi Li, Hu Long, Wenli Lai
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引用次数: 0

Abstract

Background: Orthodontic tooth movement (OTM) pain poses a significant clinical challenge, yet its underlying molecular and cellular mechanisms remain incompletely understood.

Methods: We established a mouse OTM model validated by micro-CT and histology, alongside pain assessments (Mouse Grimace Scale, bite force). Bulk RNA-seq was performed on trigeminal ganglion (TG) tissues, integrated with public single-cell RNA-seq data for a more comprehensive view, and key genes were confirmed via qPCR and immunofluorescence. A user-friendly web platform (OTMPTGTA) was developed to enable researchers to explore differentially expressed genes, gene correlations and gene-set analyses without specialised coding skills.

Results: OTM induced both significant tooth movement and heightened pain, peaking at Day 3. Transcriptomic analyses pinpointed an Atf3+ population of injured TG neurons that showed marked upregulation of xanthine dehydrogenase (Xdh) during peak pain; by Day 14, both gene expression levels and pain scores subsided. QPCR and immunofluorescence confirmed coexpression of Atf3 and Xdh at Day 3, implicating Xdh in nociceptive signalling. The OTMPTGTA platform facilitates further exploration of these and other potential pain-related pathways, offering novel insights for targeted intervention.

Conclusions: Xdh is highly expressed in Atf3+ injured neurons during OTM pain, likely intensifying nociceptive signals through oxidative and inflammatory pathways. These findings highlight Xdh as a promising therapeutic target for alleviating orthodontic pain while preserving effective tooth movement.

时间序列转录组学鉴定与正畸疼痛相关的损伤神经元中的黄嘌呤脱氢酶。
背景:正畸牙齿运动(OTM)疼痛是一个重大的临床挑战,但其潜在的分子和细胞机制仍不完全清楚。方法:建立小鼠OTM模型,通过显微ct和组织学验证,并进行疼痛评估(小鼠鬼脸量表、咬合力)。对三叉神经节(TG)组织进行Bulk RNA-seq,与公开的单细胞RNA-seq数据相结合,以获得更全面的视图,并通过qPCR和免疫荧光确认关键基因。开发了一个用户友好的网络平台(OTMPTGTA),使研究人员能够在没有专门编码技能的情况下探索差异表达基因、基因相关性和基因集分析。结果:OTM引起明显的牙齿移动和疼痛加剧,在第3天达到高峰。转录组学分析确定了Atf3+损伤的TG神经元群体,在疼痛高峰期间显示黄嘌呤脱氢酶(Xdh)的显著上调;到第14天,基因表达水平和疼痛评分均下降。QPCR和免疫荧光证实在第3天Atf3和Xdh共表达,暗示Xdh参与伤害性信号传导。OTMPTGTA平台有助于进一步探索这些和其他潜在的疼痛相关途径,为有针对性的干预提供新的见解。结论:在OTM疼痛时,Xdh在Atf3+损伤神经元中高表达,可能通过氧化和炎症途径增强伤害性信号。这些发现突出了Xdh作为一个有希望的治疗靶点,减轻正畸疼痛,同时保持有效的牙齿运动。
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来源期刊
Orthodontics & Craniofacial Research
Orthodontics & Craniofacial Research 医学-牙科与口腔外科
CiteScore
5.30
自引率
3.20%
发文量
65
审稿时长
>12 weeks
期刊介绍: Orthodontics & Craniofacial Research - Genes, Growth and Development is published to serve its readers as an international forum for the presentation and critical discussion of issues pertinent to the advancement of the specialty of orthodontics and the evidence-based knowledge of craniofacial growth and development. This forum is based on scientifically supported information, but also includes minority and conflicting opinions. The objective of the journal is to facilitate effective communication between the research community and practicing clinicians. Original papers of high scientific quality that report the findings of clinical trials, clinical epidemiology, and novel therapeutic or diagnostic approaches are appropriate submissions. Similarly, we welcome papers in genetics, developmental biology, syndromology, surgery, speech and hearing, and other biomedical disciplines related to clinical orthodontics and normal and abnormal craniofacial growth and development. In addition to original and basic research, the journal publishes concise reviews, case reports of substantial value, invited essays, letters, and announcements. The journal is published quarterly. The review of submitted papers will be coordinated by the editor and members of the editorial board. It is policy to review manuscripts within 3 to 4 weeks of receipt and to publish within 3 to 6 months of acceptance.
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