口腔医学研究 ›› 2026, Vol. 42 ›› Issue (5): 405-413.DOI: 10.13701/j.cnki.kqyxyj.2026.05.008

• 口腔正畸学研究 • 上一篇    下一篇

机械力联合RANKL增强破骨细胞NF-κB/NFATC1/TRAP信号转导促进扩弓早期骨吸收

翟荣萍1, 李晶2*   

  1. 1.内蒙古自治区人民医院口腔科 内蒙古 呼和浩特 010017;
    2.北京大学口腔医学院·口腔医院正畸科,国家口腔医学中心,国家口腔疾病临床医学研究中心,口腔生物材料和数字诊疗装备国家工程研究中心,口腔数字医学北京市重点实验室,国家卫生健康委口腔数字医学重点实验室,国家药品监督管理局口腔材料重点实验室 北京 100081
  • 收稿日期:2025-10-16 出版日期:2026-05-28 发布日期:2026-05-25
  • 通讯作者: *李晶,E-mail:Lijingchn@foxmail.com
  • 作者简介:翟荣萍(1988~ ),女,硕士,内蒙古巴彦淖尔市人,副主任医师,研究方向:骨改建生物学。
  • 基金资助:
    内蒙古自治区自然科学基金(编号:2022LHQN08005)

Mechanical Force in Conjunction with RANKL Enhances Osteoclastogenesis and Bone Resorption during Rapid Palatal Expansion by NF-κB/NFATC1/TRAP Signaling Transduction

ZHAI Rongping1, LI Jing2*   

  1. 1. Department of Stomatology, Inner Mongolia People's Hospital, Hohhot 010017, China;
    2.Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing 100081, China
  • Received:2025-10-16 Online:2026-05-28 Published:2026-05-25

摘要: 目的:探索上颌扩弓过程中早期骨吸收与破骨细胞生成的调节机制,分析核因子κB(nuclear factor kappa B,NF-κB)信号转导在这一过程中的作用。方法:选取40只8周龄雄性C57/BL6J小鼠,随机分成对照组、扩弓3 d组、扩弓5 d组、扩弓7 d组。粘接扩弓弹簧模拟上颌扩弓过程。收集样本后,使用微型计算机断层扫描(microcomputed tomography,Micro-CT)观察骨组织改建情况。进行组织切片,苏木精-伊红染色(hematoxylin-eosin,HE)染色观察组织学变化情况。使用抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色观察破骨细胞变化,同时收集组织样本提取RNA,采用实时荧光定量聚合酶链式反应(real-time quantitative polymerase chain reaction,RT-qPCR)检测破骨相关基因组织蛋白酶K(cathepsin K,Ctsk)、Trap变化。使用免疫组织化学染色观察核因子κB受体活化因子配体(receptor activator of nuclear factor kappa B ligand,RANKL)、骨保护素(osteoprotegerin,OPG)蛋白表达。使用RAW264.7细胞模拟体外加力,分组为对照组、加力组、RANKL处理组、RANKL+加力组,通过TRAP染色、免疫荧光染色及Western blot实验观察力学刺激联合RANKL处理对破骨细胞生成的调控作用,及对下游NF-κB/活化T细胞核因子1(nuclear factor of activated T cells 1,NFATC1)/TRAP信号转导的调节情况。结果:(1)扩弓机械力显著增加小鼠腭中缝宽度,诱导骨组织改建,扩弓早期至中期骨体积呈下降趋势;(2)破骨细胞数量呈现先增加后减少的时序性变化[5 d组达到峰值,(16.00±1.63)个],骨改建区域Trap与Ctsk基因表达呈先增加后减少变化趋势;(3)在扩弓中期(5 d组)RANKL表达最多[阳性细胞数(31.75±2.75)个],而OPG持续上调至扩弓末期。(4)单纯力学刺激促进RAW264.7细胞中NF-κB核转移,促进下游NFATC1、TRAP蛋白表达,力学刺激联合RANKL处理显著促进这一过程。结论:机械力联合RANKL增强破骨细胞NF-κB/NFATC1/TRAP信号转导,促进扩弓早期破骨细胞的激活和骨吸收过程。

关键词: NF-κB受体活化因子配体/骨保护素信号通路, 核因子κB, 上颌扩弓, 骨改建

Abstract: Objective: To detect the mechanism of osteoclastogenesis during palatal expansion and analyze the role of NF-κB signal transduction in this process. Methods: Forty 8-week-old male C57/BL6J mice were randomly divided into a control group, a 3-day expansion group, a 5-day expansion group, and a 7-day expansion group. Open springs were bonded to incisors to achieve palatal expansion process. After harvest, micro-CT was used to observe bone remodeling. Tissue sections were prepared and histological changes were observed by HE staining. Osteoclasts were observed by TRAP staining. Tissue samples were collected for RNA extraction, and RT-qPCR was performed to detect the expression of osteoclast-related genes Ctsk and Trap. RAW264.7 cells were used to simulate mechanical loading in vitro and divided into a control group, a force group, a RANKL treatment group, and a RANKL + force group. The regulatory effects of force combined with RANKL on osteoclastogenesis and the NF-κB/NFATC1/TRAP signaling transduction were examined by TRAP staining, immunofluorence staining, and western blot. Results: Mechanical force significantly increased the width of the palatal suture in mice and induced bone remodeling. Bone volume showed a decreasing trend from the early to middle stages of expansion. The number of osteoclasts first increased and then decreased over time, peaking in the 5-day group [(16.00±1.63) cells]. The expression of Trap and Ctsk genes also showed an initial increase followed by a decrease. RANKL expression was the highest in the middle expansion stage [5-day group, (31.75±2.75) positive cells], while OPG expression continued to increase until the late stage. Force promoted NF-κB nuclear translocation in RAW264.7 cells and increased the expression of NFATC1 and TRAP proteins. The combination of force and RANKL significantly enhanced this process. Conclusion: Mechanical force enhances the NF-κB/NFATC1/TRAP signaling transduction in osteoclasts, promoting osteoclast activation and bone resorption during the early stage of palatal expansion.

Key words: RANKL/OPG signaling pathway, NF-κB, palatal expansion, bone remodeling