Early orthodontic correction of skeletal malocclusion takes advantage of mechanical force to stimulate unclosed suture remodeling and to promote bone reconstruction; however, the underlying mechanisms remain largely unclear. Gli1⁺ cells in maxillofacial sutures have been shown to participate in maxillofacial bone development and damage repair. Nevertheless, it remains to be investigated whether these cells participate in mechanical force-induced bone remodeling during orthodontic treatment of skeletal malocclusion. In this study, rapid maxillary expansion (RME) mouse models and mechanical stretch loading cell models were established using two types of transgenic mice which are able to label Gli1⁺ cells, and we found that Gli1⁺ cells participated in mechanical force-induced osteogenesis both in vivo and in vitro. Besides, we found mechanical force-induced osteogenesis through inositol 1,4,5-trisphosphate receptor (IP₃R), and we observed for the first time that inhibition of Gli1 suppressed an increase in mechanical force-induced IP3R overexpression, suggesting that Gli1⁺ cells participate in mechanical force-induced osteogenesis through IP₃R. Taken together, this study is the first to demonstrate that Gli1⁺ cells in maxillofacial sutures are involved in mechanical force-induced bone formation through IP₃R during orthodontic treatment of skeletal malocclusion. Furthermore, our results provide novel insights regarding the mechanism of orthodontic treatments of skeletal malocclusion.

中文翻译：

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骨缝中的 Gli1+ 细胞通过 IP3R 对机械力作出反应以介导成骨

骨骼错牙合早期正畸矫正利用机械力刺激未闭合缝线重塑，促进骨重建；然而，潜在的机制在很大程度上仍不清楚。已显示颌面部缝合线中的Gli1 ⁺细胞参与颌面部骨发育和损伤修复。然而，这些细胞是否参与骨骼错牙合正畸治疗期间机械力诱导的骨重塑仍有待研究。在本研究中，使用能够标记 Gli1 ⁺细胞的两种转基因小鼠建立了快速上颌骨扩张 (RME) 小鼠模型和机械拉伸加载细胞模型，我们发现 Gli1 ⁺细胞在体内和体外都参与了机械力诱导的成骨。此外，我们通过肌醇 1,4,5-三磷酸受体 (IP ₃ R) 发现了机械力诱导的成骨，我们首次观察到 Gli1 的抑制抑制了机械力诱导的 IP3R 过表达的增加，表明 Gli1 ^{+细胞通过 IP} ₃ R参与机械力诱导的成骨。总之，本研究首次证明颌面部缝合线中的 Gli1 ^{+细胞通过 IP} ₃参与机械力诱导的骨形成骨性错牙合正畸治疗中的R。此外，我们的研究结果为骨骼错牙合正畸治疗的机制提供了新的见解。