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

根部吸收有时会通过正畸治疗，牙齿脱位，卵巢干扰，牙齿重新植入牙齿而发生，并且是牙科治疗中的大问题之一。致病细胞是基本上被认为是破骨细胞的牙牙细胞。为了研究MAPK信号在根部吸收中的作用，在M-CSF的存在下培养了骨髓巨噬细胞，并在磷酸钙涂层板上培养了骨髓巨噬细胞。在这种体外培养系统中，添加了MAPK抑制剂以查看效果。固定和陷阱染色后，计数破骨细胞和凹坑的数量。在MEK/ERK抑制剂的存在下，观察到破骨细胞数的增加。另一方面，p38mapk抑制了破骨细胞生成。然后，将MEK，ERK和P38（野生型形式和构成活性形式）转染到培养系统的细胞中。但是，没有观察到差异。然后，研究了MAPK抑制剂在破骨细胞生成中的时间效应。 p38MAPK抑制剂SB203580在分化的早期抑制了破骨细胞生成，并且在破骨细胞的后期没有影响。此外，在整骨质发生化的后期，不仅RANKL，而且不仅是TNF-Alpha，例如TNF-Alpha，脂多糖诱导的骨细胞融合，这意味着牙周炎症因子在炎症性炎症因素中增强了骨膜炎性因素，从而增强了骨膜炎症性治疗过程中的根部吸收性因素