成骨细胞凋亡抑制在介导正畸牙齿移动和牙周重塑中的作用：一项初步研究。

BACKGROUND: 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. MATERIAL AND METHODS: 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 + OTM (n=6), and group 2, IG9402 administration + OTM (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 + OTM (n=6); and group 4, IG9402 + OTM (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. RESULTS: 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. CONCLUSION: 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.

背景：正畸牙齿移动（OTM）在力应用后不久被证明会诱导牙槽骨中的破骨细胞凋亡。然而，破骨细胞凋亡如何影响正畸牙齿移动尚不清楚。本研究的目的是使用双膦酸盐类似物（IG9402）评估抑制破骨细胞形成、牙槽骨密度变化和正畸牙齿移动幅度的效果，IG9402 是一种影响破骨细胞和破骨细胞凋亡但不影响破骨细胞的药物。

材料和方法：进行了两组实验。实验 1 专门用于评估在 24 小时的 OTM 期间，IG9402 对牙槽骨中破骨细胞凋亡的影响。为此，将 12 只小鼠分为两组：组 1，生理盐水给药+OTM（n=6），组 2，IG9402 给药+OTM（n=6）。对侧未加载侧作为对照。实验 2 的目的是评估破骨细胞凋亡对 OTM 幅度和 OTM 后 10 天破骨细胞形成的作用。将 20 只小鼠分为 4 组：组 1，无 OTM 的生理盐水给药（n=5）；组 2，无 OTM 的 IG9402 给药（n=5）；组 3，生理盐水+OTM（n=6）；和组 4，IG9402+OTM（n=4）。对于这两个实验，通过超轻（25g）Sentalloy 封闭线圈弹簧在第一上颌磨牙和中切牙之间的连接来实现牙齿移动。使用 MicroCT 分析评估牙齿移动和牙槽骨密度（BVF）的线性测量。通过末端 dUTP 缺口末端标记（TUNEL）测定评估细胞死亡（或凋亡），通过抗酒石酸酸性磷酸酶（TRAP）染色和 F4/80+免疫染色评估破骨细胞和巨噬细胞的形成。

结果：我们发现，IG9402 在 OTM 后 24 小时显著抑制了牙槽骨中的破骨细胞凋亡。在 10 天，IG9402 防止了 OTM 诱导的牙槽骨密度丧失，并改变了破骨细胞和巨噬细胞的形态和质量，但对牙齿移动的幅度没有显著影响。

结论：我们的研究表明，破骨细胞凋亡可能在 OTM 期间破骨细胞和巨噬细胞形成中起重要作用，但似乎对正畸牙齿移动的幅度没有作用。