Early diagnosis of osteoarthritis using cathepsin B sensitive near-infrared fluorescent probes
Early diagnosis of osteoarthritis using cathepsin B sensitive near-infrared fluorescent probes
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DOI：
10.1016/j.joca.2003.11.005
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发表时间：
2004-03-01
影响因子：
7
通讯作者：
Tung, CH
中科院分区：
文献类型：
--
作者：
Lai, WFT;Chang, CH;Tung, CH
目的：目前骨性关节炎的诊断主要采用X线和核磁共振技术，两者都是基于组织的形态变化。然而，一旦检测到变化，组织就会出现不可逆转的缺陷。本研究利用新近研制的组织蛋白酶B敏感的近红外(NIR)荧光探针对CA的早期诊断进行了分子基础的研究。方法：12只雄性裸鼠采用右膝关节内注射胶原酶(1.0%，w/v)的方法诱导骨关节炎。左膝关节作为阴性对照。组织蛋白酶B的近红外探针被关节炎相关的组织蛋白酶B激活，从而导致发射出可在体内检测到的强烈的近红外荧光信号。在光学成像系统上采集近红外荧光信号，激发波长为610~650 nm，发射波长为680~720 nm。结果：胶原酶注射后1个月可见轻度至中度的软骨变性。小鼠的近红外荧光成像显示，静脉注射报告探针后，骨关节炎关节和正常关节24的信号强度大约相差3倍。结论：组织蛋白酶B激活的近红外荧光成像在骨性关节炎和正常关节之间存在显著差异，组织蛋白酶B激活的近红外荧光探针为早期诊断骨性关节炎提供了一种新的成像技术。(C)2003年国际骨性关节炎研究会。爱思唯尔有限公司出版。保留所有权利。
Objective: Osteoarthritis is currently diagnosed utilizing X-ray and MRI-techniques, both of which are based on the morphological changes of tissue. However, once changes are detected, the tissue has an irreversible defect. This study investigates early diagnosis of CA on a molecular basis using a recently developed cathepsin B sensitive near-infrared (NIR) fluorescent probe.Method: Twelve male nude mice were induced osteoarthritis by intra-articular injection of collagenase (1.0%, w/v) into the right knee joint. The left knee joint served as the negative control. The cathepsin B NIR probe is activated by arthritis-associated cathepsin B, thus resulting in the emission of an intensive NIR fluorescence signal which can be detected in vivo. NIR fluorescence signals were acquired on an optical imaging system using an excitation wavelength of 610-650 nm and an emission wavelength of 680-720 nm.Results: Mild to moderate degenerative cartilage was observed 1 month after collagenase injection. NIR fluorescence imaging of mice showed approximately a 3-fold difference in signal intensity between osteoarthritic and normal joints 24 In after intravenous injection of the reporter probe. Immunohistochemical evaluation also revealed cathepsin B expression in the arthritic lesion of fernorotibia joints, and not in the control contra-lateral knee joints.Conclusion: As the cathepsin B activatable NIR fluorescent imaging showed a significant difference between the osteoarthritic and normal joints, the cathepsin B activatable NIR fluorescent probe thus offers a potential new imaging technology for early OA diagnosis. (C) 2003 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.