Biologic reaction in interface tissue of aseptic loosening THA.

无菌松动THA界面组织的生物反应。

• 批准号: 07457330
• 负责人: ISHIGURO Naoki
• 金额: $ 2.75万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457330/
• 关键词: THA; cytokines; macrophage; TIMP; MMP; interface tissue

It had been clearly demonstrated that matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMPs) had important roles for tissue destruction and remodeling. we used the reverse-transcriptinal polymerase chain reaction (RT-PCR) for this study. We could detect the mRNA of MMP-1,2,3,9 and TIMP-1,2 in interface tissue. The mRNA of MMP-10 could not be detected. MMP-1 and MMP-3mRNA were observed commonly. TIMP-2mRNA were well observed, compared to TIMP-1. These observations may indicated all four enzymes cooperatively caused the undesirable bone loss around implants, and consequently resulted in failed THA.We considered that the MMPs and TIMPs play one of the critical roles for the progression of aseptic loosening of THA.Also the roles of macrophages was assessed by immunohistochemistry, electron microscopy, and molecular biological techniques. After extraction of total RNA,we used the RT-PCR to examine the expression of mRNA for IL-1a, IL-1b, TNFa, IL-8, MIP-1a, MIP-1b and MCP-1. Polyethylene debris surrounded by macrophages and phagocytosis of debris by macrophages were frequently observed in the interface tissue. Expression of chemokine mRNAs was also commonly seen, suggesting that this led to recruitment of macrophages into the bone-cement interface tissue. Macrophage activation and the production of inflammatory cytokines like IL-1 and IL-8 might induce the development of interface tissue. Debris released from implants appear to causes activation of macrophages and the production of inflammatory cytokines that induce cellular recruitment into interface tissue. This mechanism might form a vicious cycle that aggravates THA loosening.

基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）在组织破坏和重塑中起重要作用。本研究采用逆转录聚合酶链反应（RT-PCR）技术。MMP-1、2、3、9和TIMP-1、2在界面组织中的mRNA表达。MMP-10 mRNA表达阴性。MMP-1和MMP-3 mRNA在乳腺癌组织中普遍表达。TIMP-2 mRNA表达较TIMP-1明显增强。我们认为MMPs和TIMPs在THA无菌性松动的发生发展过程中起着重要作用，并通过免疫组化、电镜和分子生物学技术对巨噬细胞的作用进行了研究。提取总RNA后，采用RT-PCR检测IL-1a、IL-1b、TNF α、IL-8、MIP-1a、MIP-1b和MCP-1 mRNA的表达。在界面组织中经常观察到巨噬细胞包围聚乙烯碎片和巨噬细胞吞噬碎片。还常见趋化因子mRNA的表达，表明这导致巨噬细胞募集到骨-骨水泥界面组织中。巨噬细胞的活化和炎性细胞因子如IL-1和IL-8的产生可能诱导界面组织的发育。从植入物释放的碎片似乎会导致巨噬细胞活化和炎症细胞因子的产生，从而诱导细胞募集到界面组织中。这种机制可能形成一个恶性循环，导致THA松动。

项目成果

Naoki Ishiguro et al.: "Determination of Stromelysin-1(MMP-3), 72kDa and 92kDa Gelatinase (MMP-2,9), Tissue Inhibitor of Metalloproteinases-1(TIMP-1), and TIMP-2 in Synovial Fluid and Serum from Patients with Rheumatoid Arthritis." Journal of Rheumatology

Naoki Ishiguro 等人：“滑液和组织液中 Stromelysin-1 (MMP-3)、72kDa 和 92kDa 明胶酶 (MMP-2,9)、金属蛋白酶组织抑制剂 (TIMP-1) 和 TIMP-2 的测定

Yuichiro Yabe, Naoki Ishiguro et al.: "A perfluorochemical prevents ischemia-reperfusion injury of muscle." Journal of Surgical Research. 64. 89-94 (1996)

Yuichiro Yabe、Naoki Ishiguro 等人：“全氟化合物可预防肌肉缺血再灌注损伤。”

Naoki Ishiguro et al.: "mRNA expression of matrix metalloproteinases and tissue inhibitor of metalloproteinase in the interace tissue around implants in loosening total hip arthorplasty." Jouranal of Biomedical Matarial Research. 32. 611-617 (1996)

Naoki Ishiguro 等人：“松解全髋关节置换术中植入物周围的界面组织中基质金属蛋白酶和金属蛋白酶组织抑制剂的 mRNA 表达。”

Naoki Ishiguro et al.: "Macrophage activation and migration in interface tissue around of loosening total hip arthropathy components." Journal of Biomedical Material Research. (in press).

Naoki Ishiguro 等人：“松动的全髋关节病成分周围的界面组织中的巨噬细胞激活和迁移。”