Regulation of pathologic root resorption by control of MAPK signaling

牙根吸收常通过正畸治疗、牙齿脱位、咬合干扰、牙齿再植等方式发生，是困扰牙科治疗的一大难题。致病细胞是破牙细胞，基本上被认为是破骨细胞。为探讨MAPK信号转导通路在牙根吸收中的作用，将骨髓巨噬细胞与M-CSF和RANKL共同培养于钙磷涂层平板上。在这个体外培养体系中，加入MAPK抑制剂来观察其效果。固定后TRAP染色，计数破骨细胞数和凹陷形成情况。在MEK/ERK抑制剂存在的情况下，破骨细胞数量增加。另一方面，p38MAPK抑制破骨细胞的形成。然后，将MEK、ERK和p38(野生型和构成型)分别导入培养体系中。然而，没有观察到差异。然后，研究MAPK抑制剂在破骨细胞形成中的时间效应。P38MAPK抑制剂SB203580在分化早期抑制破骨细胞的形成，在破骨细胞分化的晚期则无作用。此外，在破骨细胞形成的晚期，不仅RANKL，而且还有其他促炎因子如肿瘤坏死因子-α、脂多糖等诱导破骨细胞融合，这表明牙周炎因子在正畸治疗和咬合创伤引起的慢性炎症环境中促进牙根吸收。

Root resorption sometimes occurs by orthodontic treatment, tooth dislocation, ooclusal interference, reimplantation of tooth, and it is one of big problems in dental treatment. The causative cells are odontoclasts that is basically thought as osteoclasts. In order to investigate the effect of MAPK signaling in root resorption, bone marrow macrophage was cultured in the presence of M-CSF and RANKL on calcium phosphate-coated plate. In this in vitro culture system, MAPK inhibitors were added to see the effect. After fixation and TRAP staining, the number of osteoclasts and pit formation were counted. In the presence of MEK/ERK inhibitors, increase of osteoclast number was observed. On the other hand, p38MAPK suppressed osteoclastogenesis. Then, MEK,ERK,and p38(wild type form and constitutive active form) were transfected into the cell of the culture system. However, the difference was not observed. Then, the time effect of MAPK inhibitors in the osteoclastogenesis was investigated. P38MAPK inhibitor SB203580 inhibited osteoclastogenesis in the early stage of differentiation, and it had no effect in the late stage of osteoclastognesis. Furthermore, in the late stage of osteoclastogenesis, not only RANKL but also other proinflammatory factors such as TNF-alpha, lipopolysaccharide induced fusion of osteoclasts, which implies periodontal inflammation factors enhance root resorption during chronic inflammatory circumstances caused by orthodontic treatment and occlusal trauma