Pang Huiqi, Ding Luhua, Che Xiaoxia
Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University, 100050, Beijing, China.
J Orofac Orthop. 2024 Dec 27. doi: 10.1007/s00056-024-00565-8.
We aimed to investigate early effects of regulating alpha‑7 nicotinic acetylcholine receptor (α7nAChR) agonists and antagonists on maxillary expansion in mice.
We allocated 36 six-week-old male C57BL/6J mice into three group: 1) expansion alone, 2) expansion plus the α7nAChR-specific agonist 3‑(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride (GTS-21), and 3) expansion plus alpha-bungarotoxin (α-BTX), a competitive antagonist of α7nAChR. The groups were daily injected with saline, GTS-21 (4 mg/kg/day) or α‑BTX (1 mg/kg/day), respectively, from days 0-7. In addition, a mouse model of maxillary expansion was established. Masson's trichrome staining was used to observe morphological changes and immunohistochemistry was performed to analyze α7nAChR, interleukin (IL)-1β, IL‑6, tumor necrosis factor (TNF)-α, runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN) expression in the midpalatal suture. Microcomputed tomography was used to measure midpalatal suture and palatal basal bone widths. We assessed the normal distribution of our data using the Kolmogorov-Smirnoff test and evaluated the homogeneity of variance by Levene's test, followed by a two-way ANOVA and Bonferroni tests at a significance level of P < 0.05.
In the GTS-21+expansion group, osteogenesis was more active in the middle palatine suture. New bone was calcified and deposited in the suture and we observed decreased IL-1β, IL‑6, and TNF‑α expression (P < 0.05). In the α‑BTX+expansion group, we observed increased proinflammatory cytokine and decreased RUNX2 and OCN expression and increased midpalatal suture and palatal basal bone widths (P < 0.05).
Using α7nAChR agonists and antagonists to regulate the cholinergic anti-inflammatory pathway, the secretion of inflammatory factors and osteoblast markers during maxillary expansion were altered, indicating the potential for clinical modulation of maxillary palatal suture expansion.
我们旨在研究调节α-7烟碱型乙酰胆碱受体（α7nAChR）激动剂和拮抗剂对小鼠上颌扩张的早期影响。
我们将36只六周龄雄性C57BL/6J小鼠分为三组：1）单纯扩张组，2）扩张加α7nAChR特异性激动剂3-（2,4-二甲氧基亚苄基）-无基底卡因二盐酸盐（GTS-21）组，3）扩张加α-银环蛇毒素（α-BTX）组，α-BTX是α7nAChR的竞争性拮抗剂。从第0天至第7天，三组小鼠分别每天注射生理盐水、GTS-21（4mg/kg/天）或α-BTX（1mg/kg/天）。此外，建立了小鼠上颌扩张模型。采用Masson三色染色观察形态学变化，并进行免疫组织化学分析腭中缝中α7nAChR、白细胞介素（IL）-1β、IL-6、肿瘤坏死因子（TNF）-α、 runt相关转录因子2（RUNX2）和骨钙素（OCN）的表达。采用微型计算机断层扫描测量腭中缝和腭基骨宽度。我们使用Kolmogorov-Smirnoff检验评估数据的正态分布，并通过Levene检验评估方差齐性，随后进行双向方差分析和Bonferroni检验，显著性水平为P<0.05。
在GTS-21+扩张组中，腭中缝的成骨更活跃。新骨在缝中钙化并沉积，我们观察到IL-1β、IL-6和TNF-α表达降低（P<0.05）。在α-BTX+扩张组中，我们观察到促炎细胞因子增加，RUNX2和OCN表达降低，腭中缝和腭基骨宽度增加（P<0.05）。
使用α7nAChR激动剂和拮抗剂调节胆碱能抗炎途径，上颌扩张过程中炎症因子和成骨细胞标志物的分泌发生改变，表明临床上对上颌腭缝扩张进行调节具有潜力。
