The effect of stress proteins that induce proinflammatory cytokines on pathological root resorption.

诱导促炎细胞因子的应激蛋白对病理根吸收的影响。

基本信息

批准号：
13672161
负责人：
HOTOKEZAKA Hitoshi
金额：
$ 2.5万
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：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672161/
关键词：
cytokine stress protein signaltransduction odontoclasts osteoclasts MEK ERK rootresorption HSP IL-1 IL-6 TNF-alpha リコンビナント歯肉溝浸出液

项目摘要

The effect of stress proteins on osteoclast (odontoclast) differentiation of preosteoclast cells (monocyte/macrophage) which was used as a in vitro model experiment of root resorption in this study. When the cells were stumulated with 100μg/ml recombinant human HSP70 and HSP90, proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha) were not induced as well as that the osteoclast differentiation was not affected. Root resorption is thought to be induced by odontoclast that is differentiated from precursor hematopeetic stem cells with the stimulation of RANKL (Receptor Activator of Nuclear Flactor kappa B Ligand) expressed on osteoblasts. Stimulation of RANKL is known to induce phospholylation of signal transduction molecules, MAPK (Mitogen Activated Ptotein Kinase) including p38 MARK and ERK (Extracellular ignal-Regulated Kinase). Then the cells were stimulated with stress proteins to investigate if the stress proteins modulate the phosphorylation of those signal transduction molecules. However, any change of phosphorylation was observed with the stimulation of stress proteins. We concluded that HSP70 and HSP90 do no induce proinflammatory cytokines in monocyte/macrophage and do not affect the osteoclast differentiation. However during in this study, a signal trasnduction pathway (MEK/ERK) was found to be very important in osteoclast differentiation. The inhibitors of MEK markedly induced osteoclast differentiation in precursor cell line, which is the first report of the inhibition of signal transduction stimulates osteoclastogenesis.

应激蛋白对骨细胞前细胞（单核细胞/巨噬细胞）的破骨细胞（Odontoclast）分化的影响，该细胞被用作本研究中根分辨率的体外模型实验。当细胞用100μg/ml重组人HSP70和HSP90浸大时，促炎细胞因子（IL-1β，IL-6，TNF-α）也未诱导，也不会受到骨细胞差异的影响。牙根分辨率被认为是由在成骨细胞上表达的RANKL（核裂纹器Kappa b配体的受体激活剂（核裂纹器kappa b配体）刺激的刺激前体血源干细胞诱导的。已知RANKL的刺激会诱导信号转导分子的磷酸化，MAPK（有丝分裂原活化的ptotoin octated Ptotoin酶），包括p38 mark和ERK（细胞外无名调节激酶）。然后用应激蛋白刺激细胞，以研究应力蛋白是否调节这些信号转导分子的磷酸化。但是，通过刺激应激蛋白观察到磷酸化的任何变化。我们得出的结论是，HSP70和HSP90在单核细胞/巨噬细胞中不会诱导促炎细胞因子，并且不会影响破骨细胞分化。但是，在这项研究中，发现信号转导途径（MEK/ERK）在破骨细胞分化中非常重要。 MEK的抑制剂显着诱导了前体细胞系中的破骨细胞分化，这是信号转导抑制的首次报道刺激了破骨细胞的发生。