Orthodontic tooth movement (OTM) has been shown to induce osteocyte apoptosis in alveolar bone shortly after force application. However, how osteocyte apoptosis affects orthodontic tooth movement is unknown. The goal of this study was to assess the effect of inhibition of osteocyte apoptosis on osteoclastogenesis, changes in the alveolar bone density, and the magnitude of OTM using a bisphosphonate analog (IG9402), a drug that affects osteocyte and osteoblast apoptosis but does not affect osteoclasts. Two sets of experiments were performed. Experiment 1 was used to specifically evaluate the effect of IG9402 on osteocyte apoptosis in the alveolar bone during 24 h of OTM. For this experiment, twelve mice were divided into two groups: group 1, saline administration + OTM24-h (n=6), and group 2, IG9402 administration + OTM24-h (n=6). The contralateral unloaded sides served as the control. The goal of experiment 2 was to evaluate the role of osteocyte apoptosis on OTM magnitude and osteoclastogenesis 10 days after OTM. Twenty mice were divided into 4 groups: group 1, saline administration without OTM (n=5); group 2, IG9402 administration without OTM (n=5); group 3, saline + OTM10-day (n=6); and group 4, IG9402 + OTM10-day (n=4). For both experiments, tooth movement was achieved using Ultra Light (25g) Sentalloy Closed Coil Springs attached between the first maxillary molar and the central incisor. Linear measurements of tooth movement and alveolar bone density (BVF) were assessed by MicroCT analysis. Cell death (or apoptosis) was assessed by terminal dUTP nick-end labeling (TUNEL) assay, while osteoclast and macrophage formation were assessed by tartrate-resistant acid phosphatase (TRAP) staining and F4/80+ immunostaining. We found that IG9402 significantly blocked osteocyte apoptosis in alveolar bone (AB) at 24 h of OTM. At 10 days, IG9402 prevented OTM-induced loss of alveolar bone density and changed the morphology and quality of osteoclasts and macrophages, but did not significantly affect the amount of tooth movement. Our study demonstrates that osteocyte apoptosis may play a significant role in osteoclast and macrophage formation during OTM, but does not seem to play a role in the magnitude of orthodontic tooth movement.

中文翻译：

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抑制骨细胞凋亡在介导正畸牙齿运动和牙周重塑中的作用：一项初步研究

已显示正畸牙齿移动 (OTM) 在施加力后不久会诱导牙槽骨中的骨细胞凋亡。然而，骨细胞凋亡如何影响正畸牙齿运动尚不清楚。本研究的目的是使用双膦酸盐类似物 (IG9402) 评估抑制骨细胞凋亡对破骨细胞生成、牙槽骨密度变化和 OTM 的影响，这是一种影响骨细胞和成骨细胞凋亡但不影响的药物。破骨细胞。进行了两组实验。实验1具体评价了IG9402对OTM 24 h内牙槽骨中骨细胞凋亡的影响。对于该实验，12 只小鼠被分为两组：第 1 组，盐水给药 + OTM24-h（n=6），第 2 组，IG9402 给药 + OTM24-h（n=6）。对侧卸载侧作为对照。实验 2 的目的是评估骨细胞凋亡对 OTM 量级和 OTM 后 10 天破骨细胞生成的作用。20只小鼠被分成4组：第1组，没有OTM的盐水给药（n=5）；第 2 组，没有 OTM 的 IG9402 给药（n=5）；第 3 组，生理盐水 + OTM10 天（n=6）；和第 4 组，IG9402 + OTM10 天（n=4）。在这两个实验中，牙齿移动是使用连接在第一颗上颌磨牙和中切牙之间的超轻 (25g) Sentalloy 封闭螺旋弹簧实现的。通过 MicroCT 分析评估牙齿运动和牙槽骨密度 (BVF) 的线性测量值。通过末端 dUTP 缺口末端标记 (TUNEL) 测定评估细胞死亡（或凋亡），而破骨细胞和巨噬细胞的形成则通过抗酒石酸酸性磷酸酶 (TRAP) 染色和 F4/80+ 免疫染色进行评估。我们发现 IG9402 在 OTM 24 小时显着阻断牙槽骨 (AB) 中的骨细胞凋亡。在第 10 天时，IG9402 阻止了 OTM 诱导的牙槽骨密度损失，并改变了破骨细胞和巨噬细胞的形态和质量，但没有显着影响牙齿移动量。我们的研究表明，骨细胞凋亡可能在 OTM 期间的破骨细胞和巨噬细胞形成中发挥重要作用，但似乎在正畸牙齿移动的幅度中没有发挥作用。IG9402 可防止 OTM 引起的牙槽骨密度损失，并改变破骨细胞和巨噬细胞的形态和质量，但对牙齿移动量没有显着影响。我们的研究表明，骨细胞凋亡可能在 OTM 期间的破骨细胞和巨噬细胞形成中发挥重要作用，但似乎在正畸牙齿移动的幅度中没有发挥作用。IG9402 可防止 OTM 引起的牙槽骨密度损失，并改变破骨细胞和巨噬细胞的形态和质量，但对牙齿移动量没有显着影响。我们的研究表明，骨细胞凋亡可能在 OTM 期间的破骨细胞和巨噬细胞形成中发挥重要作用，但似乎在正畸牙齿移动的幅度中没有发挥作用。