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Abstract：
BACKGROUND: Trans-sutural distraction osteogenesis (TSDO) involves the application of distraction force to facial sutures to stimulate osteogenesis. Gli1+ cells in the cranial sutures play an important role in bone growth. However, whether Gli1+ cells in facial sutures differentiate into bone under distraction force is unknown.
METHODS: 4-week-old Gli1ER/Td and C57BL/6 mice were used to establish a TSDO model to explore osteogenesis of zygomaticomaxillary sutures. A Gli1+ cell lineage tracing model was used to observe the distribution of Gli1+ cells and explore the role of Gli1+ cells in facial bone remodeling.
RESULTS: Distraction force promoted bone remodeling during TSDO. Fluorescence and two-photon scanning images revealed the distribution of Gli1+ cells. Under distraction force, Gli1-lineage cells proliferated significantly and co-localized with Runx2+ cells. Hedgehog signaling was upregulated in Gli1+ cells. Inhibition of Hedgehog signaling suppresses the proliferation and osteogenesis of Gli1+ cells induced by distraction force. Subsequently, the stem cell characteristics of Gli1+ cells were identified. Cell-stretching experiments verified that mechanical force promoted the osteogenic differentiation of Gli1+ cells through Hh signaling. Furthermore, immunofluorescence staining and RT-qPCR experiments demonstrated that the primary cilia in Gli1+ cells exhibit Hedgehog-independent mechanosensitivity, which was required for the osteogenic differentiation induced by mechanical force.
CONCLUSIONS: Our study indicates that the primary cilia of Gli1+ cells sense mechanical stimuli, mediate Hedgehog signaling activation, and promote the osteogenic differentiation of Gli1+ cells in zygomaticomaxillary sutures.
METHODS: 4-week-old Gli1ER/Td and C57BL/6 mice were used to establish a TSDO model to explore osteogenesis of zygomaticomaxillary sutures. A Gli1+ cell lineage tracing model was used to observe the distribution of Gli1+ cells and explore the role of Gli1+ cells in facial bone remodeling.
RESULTS: Distraction force promoted bone remodeling during TSDO. Fluorescence and two-photon scanning images revealed the distribution of Gli1+ cells. Under distraction force, Gli1-lineage cells proliferated significantly and co-localized with Runx2+ cells. Hedgehog signaling was upregulated in Gli1+ cells. Inhibition of Hedgehog signaling suppresses the proliferation and osteogenesis of Gli1+ cells induced by distraction force. Subsequently, the stem cell characteristics of Gli1+ cells were identified. Cell-stretching experiments verified that mechanical force promoted the osteogenic differentiation of Gli1+ cells through Hh signaling. Furthermore, immunofluorescence staining and RT-qPCR experiments demonstrated that the primary cilia in Gli1+ cells exhibit Hedgehog-independent mechanosensitivity, which was required for the osteogenic differentiation induced by mechanical force.
CONCLUSIONS: Our study indicates that the primary cilia of Gli1+ cells sense mechanical stimuli, mediate Hedgehog signaling activation, and promote the osteogenic differentiation of Gli1+ cells in zygomaticomaxillary sutures.
摘要：
背景：跨缝线牵张成骨（TSDO）涉及对面部缝线施加牵张力以刺激成骨。颅骨缝合线中的Gli1细胞在骨骼生长中起重要作用。然而,面部缝合线中的Gli1+细胞在牵张力下是否分化成骨未知。
方法：使用4周龄Gli1ER/Td和C57BL/6小鼠建立TSDO模型，以探讨吻合齿吻合缝的成骨作用。采用Gli1+细胞谱系示踪模型观察Gli1+细胞分布,探讨Gli1+细胞在面骨重建中的作用。
结果：牵张力促进TSDO期间的骨重建。荧光和双光子扫描图像揭示了Gli1细胞的分布。在分心的力量下，Gli1谱系细胞显著增殖并与Runx2+细胞共定位。Hedgehog信号在Gli1+细胞中上调。Hedgehog信号的抑制抑制由牵张力诱导的Gli1+细胞的增殖和成骨。随后，鉴定了Gli1+细胞的干细胞特性。细胞拉伸实验验证了机械力通过Hh信号促进Gli1+细胞的成骨分化。此外，免疫荧光染色和RT-qPCR实验表明，Gli1细胞中的初级纤毛表现出不依赖Hedgehog的机械敏感性，这是机械力诱导的成骨分化所必需的。
结论：我们的研究表明，Gli1+细胞的初级纤毛感觉到机械刺激，介导Hedgehog信号激活，促进Gli1+细胞在腋窝缝合中的成骨分化。
方法：使用4周龄Gli1ER/Td和C57BL/6小鼠建立TSDO模型，以探讨吻合齿吻合缝的成骨作用。采用Gli1+细胞谱系示踪模型观察Gli1+细胞分布,探讨Gli1+细胞在面骨重建中的作用。
结果：牵张力促进TSDO期间的骨重建。荧光和双光子扫描图像揭示了Gli1细胞的分布。在分心的力量下，Gli1谱系细胞显著增殖并与Runx2+细胞共定位。Hedgehog信号在Gli1+细胞中上调。Hedgehog信号的抑制抑制由牵张力诱导的Gli1+细胞的增殖和成骨。随后，鉴定了Gli1+细胞的干细胞特性。细胞拉伸实验验证了机械力通过Hh信号促进Gli1+细胞的成骨分化。此外，免疫荧光染色和RT-qPCR实验表明，Gli1细胞中的初级纤毛表现出不依赖Hedgehog的机械敏感性，这是机械力诱导的成骨分化所必需的。
结论：我们的研究表明，Gli1+细胞的初级纤毛感觉到机械刺激，介导Hedgehog信号激活，促进Gli1+细胞在腋窝缝合中的成骨分化。
