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

doi:10.3969/j.issn.1006-7795.2025.06.005

Abstract

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

CLC Number:

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

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