Immunohistochemical distribution of advanced glycation end products (AGEs) in human osteoarthritic cartilage
Immunohistochemical distribution of advanced glycation end products (AGEs) in human osteoarthritic cartilage
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DOI：
10.1016/j.acthis.2010.06.007
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发表时间：
2011-01-01
影响因子：
2.5
通讯作者：
Mizuta, Hiroshi
中科院分区：
文献类型：
--
作者：
Hirose, Jun;Yamabe, Soichiro;Mizuta, Hiroshi
晚期糖基化终产物（AGES）可能与骨关节炎（OA）有关，因为AGES在关节软骨中的积聚是最显著的年龄相关变化之一。AGEs修饰组织蛋白质的结构和功能，并刺激由AGEs特异性受体（AGEs）介导的细胞反应。本研究使用新鉴定的表位特异性抗体研究了AGEs在退变软骨中的定位，以确定AGEs的分布与OA的发生和进展之间的联系。对OA患者胫骨平台骨软骨标本进行N（N）-（羧甲基）赖氨酸（CML）、N（N）-（羧乙基）赖氨酸（CEL）、戊糖苷、GA-吡啶和N（N）-（羧乙基）赖氨酸特异性抗体免疫染色。这些表位的免疫组织化学分布进行了评价软骨退变。AGEs和AGEs的免疫反应性（IR）在细胞内比在细胞外基质中更强。与肉眼可见的完整软骨相比，在轻度和重度OA软骨中观察到细胞CML和CEL的IR更高。GA-吡啶和吲哚乙酸在IR随OA等级增加的模式中有很强的关联。这些随软骨退变而变化的AGEs IR图谱表明，AGE修饰的蛋白与软骨退变有关。GA-吡啶和AGEs的一致上调表明GA-吡啶是通过AGEs途径导致软骨退变的最重要的AGE。(C)2010年Elsevier GmbH。All rights reserved.
Advanced glycation end products (AGES) may be associated with osteoarthritis (OA), because the accumulation of AGEs in articular cartilage are among the most striking age-related changes. AGEs modify the tissue protein structure and function and stimulate the cellular responses mediated by a specific receptor for AGEs (RAGE). This study investigated the localization of AGEs in degenerated cartilage using newly identified epitope-specific antibodies to determine the linkage between the distribution of AGEs and the development and progression of OA. Osteochondral specimens of the tibial plateau from OA patients were immunostained by specific antibodies against N(epsilon)-(carboxymethyl)lysine (CML), N(epsilon)-(carboxyethyl)lysine (CEL), pentosidine, GA-pyridine, and RAGE. The immunohistochemical distribution of these epitopes was evaluated during cartilage degeneration. The immunoreactivity (IR) of AGEs and RAGE was stronger in cells rather than in the extracellular matrix. Higher IR of cellular CML and CEL was observed in both mild and severe OA cartilage in comparison to macroscopically intact cartilage. There was a strong association between GA-pyridine and RAGE in the pattern of increasing IR with the OA grade. These IR patterns of AGEs varying with cartilage degeneration indicate that AGE modified proteins are associated with cartilage degeneration. The coincidental up-regulation of GA-pyridine and RAGE suggests that GA-pyridine is the most significant AGE for cartilage degeneration via the RAGE pathway. (C) 2010 Elsevier GmbH. All rights reserved.