Functional analysis of plasminogen related genes in cartilage metabolism

软骨代谢中纤溶酶原相关基因的功能分析

基本信息

批准号：
18591677
负责人：
MORIOKA Hideo
金额：
$ 2.23万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591677/
关键词：
Joint disease Rheumatoid arthritis Osteoarthritis Bone and Cartilage metabolism Angiogenesis Cartilage Synovium Synovitis

项目摘要

The purpose of this study is to clarify the role of PRGB and PRPB in arthritis joint such as RA. We investigated the expression of PRGB and the role of PRPB in the main components, synovium and cartilage, in rheumatoid arthritis closely involving angiogenesis. PRGB was not expressed in synoviocytes under normal conditions in vitro, and expression was not induced, even when the cells were stimulated with cytokines (IL-1 and bFGF) to mimic a condition similar to rheumatoid arthritis. In cartilage, PRGB was not expressed in chondrocytes under normal conditions, but the expression was enhanced by cytokine stimulation. On ISH, PRGB was not expressed in the synovial membrane, but was partially expressed in joint cartilage with RA. These findings suggested that PRGB is not expressed in normal joint cartilage, but that the expression is enhanced when stimulated, such as during inflammation, although the mechanism remains unclear. To investigate the action of PRGB, we prepared the recombinant P … More RGB protein (PRPB). In RA, the influence of PRPB on synoviocytes was investigated because synovium growth is involved in the pathogenesis. Synoviocytes proliferated when stimulated with cytokines (IL-1 and bFGF). However, PRPB did not inhibit the proliferation. Thus, we focused on the hypothesis that VEGF could strongly induce new blood vessel formation in inflammatory synovium in RA, and investigated the influence of PRPB on VEGF expression. Firstly, we added PRPB to synoviocytes and chondrocytes stimulated with cytokines (IL-1 and bFGF), and investigated the changes in VEGF expression at the gene and protein levels. PRPB significantly inhibited VEGF expression in synoviocytes at both the gene and protein levels, and in cartilage at the gene level. For in vivo study, CIA mice that are presumed to represent the pathology of rheumatoid arthritis were used. The paw thickness was significantly reduced over the time in the PRPB treatment group, compared to that in the control group treated with PBS. In addition, bone erosion and destruction were reduced on micro CT. Histopathologically, synovium growth and bone destruction were both reduced, and the number of CD31-positive vascular endothelial cells was also decreased on immunostaining of vascular endothelial cells in the articular synovial tissue with anti-CD31 antibody. It was suggested that arthritis was inhibited and angiogenesis was suppressed in the PRPB treatment group. Regarding the action of PRPB on vascular endothelial cells, the inhibitory effect was exerted via integrin. It was also suggested that inhibition of VEGF produced by the synovial tissue suppressed angiogenesis. The mechanism of action of the inhibition of VEGF by PRPB remains to be investigated. This study confirmed that PRPB inhibits arthritis by suppressing angiogenesis, but many of the details of the mechanism of action are unclear and remain to be investigated. Less

PRGB和PRPB在关节炎中的作用，例如主要成分，滑膜和软骨，在类风湿关节炎中均未诱导prgb。是类似于软骨中的类似于类似的疾病，在正常条件下，在软骨细胞中未表达PRGB，但是在ISH上，PRGB在PRGB中未表达，pRGB在prgb中未表达，prgb在prgb中没有表达，pRGB在prgb中未表达，prgb在prgb中未表达，prgb在prgb中未表达，prgb在prgb中未表达，prgb却没有表达，prgb却没有表达，pRGB在prgb中未表达，则PRGB在prgb中没有表达，prgb bess sss sss sss sss sss sss sss sss sss sss sss sss sss ssed，则是stithokines。与RA的关节软骨。）。 RA中的炎性滑膜形成，并研究了PRPB对VEGF Express的影响。在体内研究的基因水平生长和骨骼破坏都减少了，CD31阳性的血管内皮细胞的数量也被降低，这也降低了抗CD31抗体的关节组织中的血管射精组织的免疫抑制作用。 PRPB治疗组是通过整合素施加的。通过抑制血管生成，但是作用机理的许多细节尚不清楚，并且仍在研究。