基于间质微环境--破骨细胞相互作用优化AOO应用的实验动物学研究

Accelerated osteogenic orthodontics (AOO), a corticotomy-facilitated orthodontic treatment, could significantly decreases the therapeutic duration, which could be the best news for orthodontic treatment patients. But the risk of pain, swelling and the destruction in the alveolar bone due to the extra operation, as well as the additional cost, serious influence the application of AOO. Therefore, the improvement, and even the substitutes of AOO are worthy of exploring. ..Our previous studies demonstrated that the acceleration of tooth movement perhaps could be mainly attributed to the effects of absorption in the local alveolar bone, instead of the osteogenic effects which remained inconspicuous throughout the experiment. During the AOO, osteoclasts continued to differentiate and be activated, displayed the maximum of osteoclasts counting in at least two timepoints, as well as the expression of various exclusively osteoclastogenic markers; however, the control groups underwent traditional orthodontics displayed inconspicuous tendency of osteoclastogenesis. ..Furthermore, the continuous osteoclastogenesis during AOO treatment seemed associated with local stroma fibroblasts in alveolar bone. On the orther hand, the interactions between fibroblasts and the osteoclasts precursor were focused in recent years. In our previous studies, the conditioned medium collected from the local alveolar fibroblasts of AOO animal model induced significantly more osteoclasts, compared to that from the animal underwent traditional orthodontics. It suggested that the osteoclasts differentiation and activation was regulated by the local stroma fibroblasts in alveolar bone, it was consistent with many recent reports that fibroblast influence osteoclastogenesis in both the pathological and physiological conditions...Therefore, it is very important to understand the mechanism of paracrine regulating the osteoclastogenesis in AOO. On this basis, the treatments without injury, such as ultrasound, temperature alteration or electrical pulse, would be used to make fibroblast express the similar paracrine in AOO, for the purpose of accelerating orthodontics treatment.

加速成骨正畸（accelerated osteogenic orthodontics AOO）是一种通过牙槽骨皮质切开辅助显著缩短正畸疗程的治疗方式，是广大正畸患者的极大利好，但其分子生物学机制并不完全清晰，且额外增加的手术操作、风险和花费，严重影响其推广应用，探寻AOO细胞分子学机制，创新优化或替代方案十分必要。本课题组前期研究证实，AOO加速牙齿移动过程可能更多依赖破骨作用；表现为局部牙槽骨中破骨细胞的持续分化，且出现2次峰值；这种持续分化现象与局部间质成纤维细胞旁分泌作用密切相关。因此，本研究需进一步明确AOO条件下，间质成纤维细胞如何以旁分泌方式调控破骨细胞增殖；在此基础上，通过无创性物理刺激，重现类似的旁分泌-破骨细胞调控作用；并尝试应用于动物体内，寻求优化甚至替代AOO治疗。

本研究是在前期研究的基础上的进一步研究，前期研究证实，AOO加速牙齿移动过程可能更多依赖破骨作用，表现为局部牙槽骨中破骨细胞的持续分化，且出现2次峰值， 本研究进一步证实了这种持续分化现象与局部间质成纤维干细胞旁分泌作用有关；基因检测证实，M-CSF在此过程中发挥重要作用；高强度高频率短暂超声波刺激能重现类似的旁分泌-破骨细胞调控作用，有希望模拟甚至代替ＡＯＯ加速正畸牙移动。