CaSR介导Gli1+骨骼干细胞在颌骨稳态调控中的作用

doi:10.3969/j.issn.1006-7795.2025.06.005

首都医科大学学报 ›› 2025, Vol. 46 ›› Issue (6): 984-991.doi: 10.3969/j.issn.1006-7795.2025.06.005

CaSR介导Gli1⁺骨骼干细胞在颌骨稳态调控中的作用

魏雅莉^1,2，吕平^1,2，黎祖岑^1,2，张琪^1,2，陈馨语^1,2，徐若诗^1,2，袁泉^1,3，周陈晨^1,4，樊怡^1,2*

1.口腔疾病防治全国重点实验室国家口腔医学中心国家口腔疾病临床医学研究中心，成都 610041；2. 四川大学华西口腔医院牙体牙髓病科，成都 610041；3. 四川大学华西口腔医院种植科，成都 610041；4. 四川大学华西口腔医院儿童口腔科，成都 610041

收稿日期:2025-08-13 修回日期:2025-09-24 出版日期:2025-12-21 发布日期:2025-12-19
通讯作者: 樊怡 E-mail:yifan@scu.edu.cn
基金资助:
国家自然科学基金项目（82370945），四川省自然科学基金项目（2024NSFSC0545）。

Role of CaSR in Gli1⁺ skeletal stem cells in the regulation of mandibular homeostasis

Wei Yali^1,2，Lyu Ping^1,2，Li Zucen^1,2，Zhang Qi^1,2，Chen Xinyu^1,2，Xu Ruoshi^1,2，Yuan Quan^1,3，Zhou Chenchen^1,4，Fan Yi^1,2*

1.State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; 2. Department of Cariology and Endodontics, West China Hospital of Stomatology, Chengdu 610041, China；3. Department of Oral Implantology, West China Hospital of Stomatology, Chengdu 610041, China；4. Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China

Received:2025-08-13 Revised:2025-09-24 Online:2025-12-21 Published:2025-12-19
Supported by:
This study was supported by National Natural Science Foundation of China (82370945), Natural Science Foundation of Sichuan Province (2024NSFSC0545).

摘要/Abstract

摘要： 目的明确神经胶质瘤相关癌基因锌指蛋白1（glioma-associated oncogene homolog 1, Gli1）阳性的骨骼干细胞（skeletal stem cells，SSCs）特异性表达的钙敏感受体（calcium-sensing receptor, CaSR）在颌骨稳态中的调控作用。方法利用Cre-loxp系统构建Gli1^CreER;CaSR^fl/fl;Rosa26^Ai14转基因小鼠模型，对照组小鼠为Gli1^CreER;CaSR^fl/+;Rosa26^Ai14。3周龄时给与小鼠腹腔注射他莫昔芬，6周后收取下颌骨进行小动物计算机体层显像仪扫描。通过苏木素/伊红染色明确颌骨及牙周组织的改变，免疫荧光染色明确成骨及破骨活动变化。结果本研究成功构建Gli1⁺骨骼干细胞特异性CaSR敲除小鼠，与对照小鼠相比，Gli1^CreER;CaSR^fl/fl;Rosa26^Ai14小鼠颌骨骨量上调，骨体积分数和骨小梁厚度显著增加、骨小梁分离度显著下降。HE染色显示突变鼠颌骨骨组织致密，COL1、OSX蛋白表达显著上升，TRAP⁺破骨细胞数目明显下降，牙周膜纤维结构和排列未见明显改变。结论 Gli1⁺ SSCs特异性CaSR缺失导致颌骨骨量上调，促进成骨活动，抑制破骨功能。明确了CaSR调控SSCs参与颌骨稳态维持的作用，为颌面部骨缺损疾病的治疗提供了潜在靶点。

关键词: 转基因小鼠, 发育, 成骨分化, 骨形成, 骨吸收, 微环境

Abstract: Objective To investigate the role of the calcium-sensing receptor (CaSR) in glioma-associated oncogene homolog 1 (Gli1）+ skeletal stem cells (SSCs) in mandibular bone homeostasis.Methods Gli1^CreER;CaSR^fl/fl;Rosa26^Ai14 and Gli1^CreER;CaSR^fl/+;Rosa26^Ai14 mice were generated. Tamoxifen was intraperitoneally administered to 3-week-old male mice, and the mandibles were harvested 6 weeks after induction. Micro-computed tomography was used to analyze the alveolar bone at the root bifurcation region of the first mandibular molar. Hematoxylin and eosin (HE) staining was performed to analyze the changes of mandibles and periodontal tissue. Immunofluorescence staining was used to investigate the changes in bone formation and bone resorption activities.Results Gli1⁺ SSCs-specific CaSR knockout mice were successfully generated. Compared to controls, Gli1^CreER;CaSR^fl/fl;Rosa26^Ai14 mice exhibited a significant increase in alveolar bone mass, characterized by higher bone volume fraction, increased trabecular thickness, and decreased trabecular separation. HE staining showed a denser bone microarchitecture in the mutant mice, accompanied by elevated expression of COL1 and OSX while the number of TRAP⁺ osteoclasts was significantly decreased. Notably, the structure and organization of periodontal ligament fibers remained comparable.Conclusions Targeted ablation of CaSR in Gli1⁺ SSCs promoted alveolar bone formation by enhancing osteogenic activity of Gli1⁺ SSCs while suppressing osteoclastic function. These findings underscore a pivotal role for CaSR in modulating SSCs function during mandibular homeostasis and reveal its potential as a therapeutic target for craniofacial bone regeneration.

Key words: transgenic mouse, development, osteogenic differentiation, bone formation, bone resorption, microenvironment

中图分类号:

魏雅莉, 吕平, 黎祖岑, 张琪, 陈馨语, 徐若诗, 袁泉, 周陈晨, 樊怡. CaSR介导Gli1⁺骨骼干细胞在颌骨稳态调控中的作用[J]. 首都医科大学学报, 2025, 46(6): 984-991.

Wei Yali, Lyu Ping, Li Zucen, Zhang Qi, Chen Xinyu, Xu Ruoshi, Yuan Quan, Zhou Chenchen, Fan Yi. Role of CaSR in Gli1⁺ skeletal stem cells in the regulation of mandibular homeostasis[J]. Journal of Capital Medical University, 2025, 46(6): 984-991.

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CaSR介导Gli1⁺骨骼干细胞在颌骨稳态调控中的作用

Role of CaSR in Gli1⁺ skeletal stem cells in the regulation of mandibular homeostasis

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CaSR介导Gli1+骨骼干细胞在颌骨稳态调控中的作用

Role of CaSR in Gli1+ skeletal stem cells in the regulation of mandibular homeostasis

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CaSR介导Gli1⁺骨骼干细胞在颌骨稳态调控中的作用

Role of CaSR in Gli1⁺ skeletal stem cells in the regulation of mandibular homeostasis