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Regulation of pathologic root resorption by control of MAPK signaling

通过控制 MAPK 信号传导调节病理根吸收

基本信息

批准号：
15592169
负责人：
HOTOKEZAKA Hitoshi
金额：
$ 2.24万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15592169/
关键词：
odontoclasts osteoclasts root resorption MAPK MEK ERK p38 RANKL differentiation

项目摘要

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

正畸治疗、牙脱位、卵母细胞干扰、牙再植等均会引起牙根吸收，是牙科治疗中的一大难题。致病细胞是破牙细胞，基本上被认为是破骨细胞。为了研究MAPK信号在牙根吸收中的作用，在磷酸钙包被的平板上培养骨髓巨噬细胞，在M-CSF和RANKL的存在下。在该体外培养系统中，加入MAPK抑制剂以观察效果。固定后，TRAP染色，计数破骨细胞数和陷窝形成。在MEK/ERK抑制剂存在下，观察到破骨细胞数量增加。另一方面，p38 MAPK抑制破骨细胞的生成。然后，将MEK、ERK和p38（野生型形式和组成型活性形式）转染到培养系统的细胞中。然而，未观察到差异。然后，研究MAPK抑制剂在破骨细胞生成中的时间效应。P38 MAPK抑制剂SB 203580在破骨细胞分化早期抑制破骨细胞的生成，在破骨细胞分化晚期则无影响。此外，在破骨细胞生成的晚期，不仅RANKL，而且其他促炎因子如TNF-α、脂多糖也可诱导破骨细胞融合，这意味着在正畸治疗和咬合创伤引起的慢性炎症环境中，牙周炎症因子可促进牙根吸收