Mechanosensing by Gli1+ cells contributes to the orthodontic force-induced bone remodelling
Mechanosensing by Gli1+ cells contributes to the orthodontic force-induced bone remodelling
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DOI：
10.1111/cpr.12810
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发表时间：
2020-04-23
影响因子：
8.5
通讯作者：
Jin, Fang
中科院分区：
文献类型：
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作者：
Liu, An-Qi;Zhang, Li-Shu;Jin, Fang
Gli1（+）细胞在组织稳态和损伤动员中受到广泛关注。本研究的目的是研究Gli1（+）细胞是否对力有反应并有助于骨重塑。材料与方法建立正畸牙齿运动（OTM）模型，评估骨对机械力的响应。利用转基因小鼠分别标记和抑制Gli1（+）细胞。此外，本研究应用小鼠条件消融Gli1（+）细胞中的yes相关蛋白（Yap）。分析了牙的运动和骨的重塑。结果Gli1（+）细胞首次在牙周韧带（PDL）中表达。它们在张力作用下增殖分化为成骨细胞。接下来，利用药理学和遗传学的Gli1抑制模型来证实Gli1（+）细胞的抑制导致骨重塑的停止。此外，免疫荧光染色发现经典的机械转导因子Yap在Gli1（+）细胞中表达，并在Gli1（+）细胞抑制后降低。此外，条件消融Gli1（+）细胞中的Yap基因也抑制了骨重塑，表明Gli1（+）细胞是力响应细胞。结论PDL中Gli1（+）细胞直接响应正畸力并介导骨重构，为骨重构机制提供了新的功能证据，首次揭示了Gli1（+）细胞的力学响应特性。
Objectives Gli1(+) cells have received extensive attention in tissue homeostasis and injury mobilization. The aim of this study was to investigate whether Gli1(+) cells respond to force and contribute to bone remodelling.Materials and methods We established orthodontic tooth movement (OTM) model to assess the bone response for mechanical force. The transgenic mice were utilized to label and inhibit Gli1(+) cells, respectively. Additionally, mice that conditional ablate Yes-associated protein (Yap) in Gli1(+) cells were applied in the present study. The tooth movement and bone remodelling were analysed.Results We first found Gli1(+) cells expressed in periodontal ligament (PDL). They were proliferated and differentiated into osteoblastic cells under tensile force. Next, both pharmacological and genetic Gli1 inhibition models were utilized to confirm that inhibition of Gli1(+) cells led to arrest of bone remodelling. Furthermore, immunofluorescence staining identified classical mechanotransduction factor Yap expressed in Gli1(+) cells and decreased after suppression of Gli1(+) cells. Additionally, conditional ablation of Yap gene in Gli1(+) cells inhibited the bone remodelling as well, suggesting Gli1(+) cells are force-responsive cells.Conclusions Our findings highlighted that Gli1(+) cells in PDL directly respond to orthodontic force and further mediate bone remodelling, thus providing novel functional evidence in the mechanism of bone remodelling and first uncovering the mechanical responsive property of Gli1(+) cells.