The working mechanism of bone resorption inhibitory protein induced by osteoclasts

破骨细胞诱导骨吸收抑制蛋白的作用机制

基本信息

批准号：
15390648
负责人：
NOGUCHI Toshihide
金额：
$ 8.06万
依托单位：
Aichi-Gakuin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390648/
关键词：
OIP-1 IFN-γ Periodontitis Bone resorption Osteoclast IL-1β

项目摘要

Periodontitis is a chronic inflammatory disease caused by infections with Gram-negative bacteria and characterized by alveolar bone resorption. It is very critical to inhibit bone resorption for treatment and prevention of periodontitis. The osteoclast (OCL) is the primary bone resorbing cell and there are many reports about intracellular signaling pathway related with OCL differentiation. It is possible to control bone resorption if we could manage this signaling pathway. Our collaborator identified OCL inhibitory peptide-1 (OIP-1/hSca) as a novel inhibitor of OCL formation and bone resorption that is produced by OCLs. OIP-1 is a unique protein from OCLs to be able to inhibit OCL differentiation by itself. Our main object of this study is to seek the possibility for clinical application of OIP-1 in periodontitis by expoloring the mechanism of this OCL inhibition. We used cycle-dependent reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, which demonstrated that interfer … More on-γ (IFN-γ) strongly enhanced OIP-1/hSca mRNA expression in mouse bone marrow cells and osteoblasts. Similarly, interleukin (IL)-12 also enhanced OIP-1 mRNA expression. To determine the participation of OIP-1 in IFN-γ inhibition of OCL formation, we tested the capacity of a neutralizing antibody specific to OIP-1 c-peptide to inhibit IFN-γ's effects on OCL-like cell differentiation of mouse macrophages, RAW 264.7 cells. Anti-OIP-1 c-peptide specific antibody partially neutralized IFN-γ inhibition of OCL differentiation. Furthermore, OIP-1 inhibited phospho-c-Jun (p-c-Jun) kinase activity in RAW 264.7 cells. However, OIP-1/hSca did not affect NF-κB activation hi these cells. Western blot analysis further demonstrated that OIP-1 significantly decreased TNF receptor associated factor 2 (TRAF-2) expression in RAW 264.7 cells. However, OIP-1 had no effect on TRAF-6 expression in these cells. These data show that IFN-γ enhances OIP-1/hSca expression in mouse bone marrow cells and osteoblasts, and that OIP-1 inhibits OCL formation through suppression of TRAF-2 and p-c-Jun kinase activity. These findings suggest the possibility by OIP-1 to inhibit inflammatory bone resorption in periodontitis Less

牙周炎是由革兰氏阴性细菌引起的慢性炎症性疾病，并以肺泡吸收为特征。许多细胞内的报告。 S。在小鼠骨髓细胞和成骨细胞中增强的OIP-1/HSCA mRNA，我们测试了特异性的OIP-1 C肽中和抗体的能力，以抑制对OCL样细胞的影响巨噬细胞264.7细胞部分中和IFN抑制了OCL的分化。 -1显着降低了TNF的TNF招募因子2（TRAF-2）在RAW 264.7细胞中的表达，但OIP-1对这些细胞中的Traf-6表达没有影响。 OIP-1抑制了Traf-2和P-C-Jun激酶的作用，这些发现也表明了OIP-1的可能性。