氟中毒对大鼠正畸牙移动中破骨细胞活性及RANK/RANKL/OPG通路表达的影响

doi:10.13701/j.cnki.kqyxyj.2025.07.007

摘要/Abstract

摘要： 目的: 通过监测破骨细胞活性变化及核因子κB受体活化因子(receptor activator of nuclear factor-κB, RANK)/核因子受体激活因子-κB配体(receptor activator of nuclear factor-κB ligand, RANKL)/骨保护素(osteoprotegerin, OPG)通路表达水平,探讨慢性氟中毒对大鼠正畸牙移动的影响。方法: 将80只SD大鼠随机分为4组:对照组、正畸组、染氟组和染氟正畸组,每组进一步分为3、7、14和21天亚组(每亚组5只)。建立氟中毒和正畸牙移动模型后,通过抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase, TRAP)染色检测破骨细胞数,免疫组织化学和实时荧光定量聚合酶链反应(polymerase chain reaction,PCR)分析RANKL、OPG和RANK的蛋白及mRNA表达水平。结果: ①成功建立了慢性氟中毒和正畸牙移动模型;②正畸后大鼠TRAP阳性破骨细胞数显著增加(P<0.05),但染氟正畸组显著低于正畸组(P<0.05);③染氟正畸组RANK表达高于染氟组(P<0.05),但与正畸组无显著差异(P>0.05),RANKL表达在正畸组最高,显著高于染氟正畸组(P<0.05),正畸组的OPG表达最高,尤其在初始阶段(P<0.05);④染氟组RANKL/OPG比率低于对照组(P<0.05),正畸组比率高于染氟正畸组;⑤慢性氟中毒大鼠正畸牙移动符合典型的 “快速-迟缓-回升”周期特征,染氟正畸组初始阶段速率低于正畸组(P<0.05),后期无显著差异。结论: 氟积累通过调控RANK/RANKL/OPG通路表达,降低破骨细胞活性,最终限制正畸牙移动速率。

关键词: 氟中毒, 正畸牙移动, 破骨细胞, RANK/RANKL/OPG通路

Abstract: Objective: To investigate the impact of chronic fluorosis on orthodontic tooth movement (OTM) in rats by assessing alterations in osteoclast activity and the expression levels of receptor activator of nuclear factor-κB (RANK)/receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG). Methods: Eighty SD rats were evenly divided into four groups using a random number table: control group, orthodontic group, fluoridated group, and fluoridated orthodontic group with each group divided into 3-day, 7-day, 14-day, and 21-day subgroups (n=5/subgroup). After establishing the fluorosis and OTM models, osteoclast counts were determined via tartrate-resistant acid phosphatase (TRAP) staining. Protein and mRNA expression levels of RANKL, OPG, and RANK were analyzed using immunohistochemistry and real-time fluorescence quantitative PCR. Results: Rats in the fluoridated group exhibited grade Ⅱ-Ⅲ dental fluorosis, with fluoride levels higher than control group (P<0.05). After orthodontic treatment, a significant gap appeared between the first and second molars of the mice, indicating the successful establishment of chronic fluorosis and OTM models. TRAP-positive osteoclasts were significantly increased in mice after orthodontic treatment (P<0.05), while fluoridated orthodontic group had significantly fewer osteoclasts than the orthodontic group (P<0.05). RANK expression in fluoridated orthodontic group was higher than that in fluoridated group (P<0.05), but not significantly different from that in orthodontic group (P>0.05). RANKL expression was the highest in orthodontic group, and higher than that in fluoridated orthodontic group (P<0.05). OPG expression was the highest in orthodontic group, particularly in the initial stage (P<0.05). The RANKL/OPG ratio in fluoridated group was lower than that in control group (P<0.05), and orthodontic group had a higher ratio than fluoridated orthodontic group. Mice with chronic fluorosis exhibited a typical "fast-slow-rebound" cycle of orthodontic tooth movement, with fluoridated orthodontic group featuring lower initial velocity than orthodontic group (P<0.05), and no significant difference in later stages. Conclusion: Fluoride accumulation affects the expression of RANK/RANKL/OPG, reduces osteoclast activity, and ultimately restricts orthodontic tooth movement.

Key words: fluorosis, orthodontic tooth movement, osteoclast, RANK/RANKL/OPG pathway

梁会敏, 贾莹, 丁雪, 刘纯. 氟中毒对大鼠正畸牙移动中破骨细胞活性及RANK/RANKL/OPG通路表达的影响[J]. 口腔医学研究, 2025, 41(7): 581-588.

LIANG Huimin, JIA Ying, DING Xue, LIU Chun. Effects of Fluorosis on Osteoclast Activity and RANK/RANKL/OPG Pathway Expression during Orthodontic Tooth Movement in Mice[J]. Journal of Oral Science Research, 2025, 41(7): 581-588.

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