Trigeminal neurons control immune-bone cell interaction and metabolism in apical periodontitis.
Trigeminal neurons control immune-bone cell interaction and metabolism in apical periodontitis.
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DOI：
10.1007/s00018-022-04335-w
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发表时间：
2022-05-31
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根尖周炎（AP）是牙齿感染后发生的一种炎症性疾病，具有明显的溶骨活性。尽管越来越多的证据表明感觉神经元参与非神经元细胞的调节，但它们在 AP 发展中的作用很大程度上未知。我们假设三叉神经节 (TG) Nav1.8+ 伤害感受器调节骨代谢变化以响应 AP。通过选择性消融 Nav1.8Cre/白喉毒素 A (DTA)Lox 小鼠系中的伤害性神经元，使用感染诱导的 AP 小鼠模型来评估 AP 的发生和进展。 Nav1.8+伤害感受器的消融使AP进展更早，溶骨性病变更大。免疫组织化学和 RNAscope 分析表明，Nav1.8Cre/DTALox 小鼠中早期时间点的巨噬细胞、T 细胞、破骨细胞和成骨细胞前体数量较多，并且 RANKL:OPG 比率增加。伤害感受器消除小鼠的病灶内 IL-1α 和 IL-6 的表达增加。此外，共培养实验表明，TG 神经元促进成骨细胞矿化并抑制破骨细胞功能。研究结果表明，TG Nav1.8+ 神经元通过延迟免疫细胞的流入、促进成骨细胞分化和降低破骨细胞活性来调节 AP 发育。这种新发现的机制可能成为治疗 AP 的一种治疗策略，并最大限度地减少难治性病例中溶骨性病变的持续存在。在线版本包含可在 10.1007/s00018-022-04335-w 获取的补充材料。
Apical periodontitis (AP) is an inflammatory disease occurring following tooth infection with distinct osteolytic activity. Despite increasing evidence that sensory neurons participate in regulation of non-neuronal cells, their role in the development of AP is largely unknown. We hypothesized that trigeminal ganglia (TG) Nav1.8+ nociceptors regulate bone metabolism changes in response to AP. A selective ablation of nociceptive neurons in Nav1.8Cre/Diphtheria toxin A (DTA)Lox mouse line was used to evaluate the development and progression of AP using murine model of infection-induced AP. Ablation of Nav1.8+ nociceptors had earlier progression of AP with larger osteolytic lesions. Immunohistochemical and RNAscope analyses demonstrated greater number of macrophages, T-cells, osteoclast and osteoblast precursors and an increased RANKL:OPG ratio at earlier time points among Nav1.8Cre/ DTALox mice. There was an increased expression of IL-1α and IL-6 within lesions of nociceptor-ablated mice. Further, co-culture experiments demonstrated that TG neurons promoted osteoblast mineralization and inhibited osteoclastic function. The findings suggest that TG Nav1.8+ neurons contribute to modulation of the AP development by delaying the influx of immune cells, promoting osteoblastic differentiation, and decreasing osteoclastic activities. This newly uncovered mechanism could become a therapeutic strategy for the treatment of AP and minimize the persistence of osteolytic lesions in refractory cases. The online version contains supplementary material available at 10.1007/s00018-022-04335-w.
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影响因子：
5.3
作者：
Diogenes, Anibal;Patwardhan, Amol M.;Hargreaves, Kenneth M.
通讯作者：
Hargreaves, Kenneth M.
影响因子：
4.8
作者：
Ecarot, B;Desbarats, M
通讯作者：
Desbarats, M
影响因子：
3.2
作者：
Bord, S;Ireland, DC;Compston, JE
通讯作者：
Compston, JE
影响因子：
3.4
作者：
He, Haitao;Chai, Jianshen;Yang, Zhenzhou
通讯作者：
Yang, Zhenzhou
DOI：
10.1016/0030-4220(65)90166-0
发表时间：
1965-01-01
期刊：
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY
影响因子：
--
作者：
KAKEHASHI, S;STANLEY, HR;FITZGERALD, RJ
通讯作者：
FITZGERALD, RJ