Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability
Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability
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DOI：
10.1016/j.joca.2015.11.008
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发表时间：
2016-04-01
影响因子：
7
通讯作者：
Saito, T.
中科院分区：
文献类型：
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作者：
Chang, S. H.;Yasui, T.;Saito, T.
目的：踝关节骨关节炎（OA）的患病率低于膝关节OA，然而，这种差异的分子机制尚未揭示。在本研究中，我们开发了小鼠踝关节OA模型作为工具，以调查踝关节OA的病理生理学和踝关节软骨的分子特征。设计：我们解剖学和组织学检查踝关节和膝关节的C57 BL/6小鼠，并将它们与人类样本进行比较。我们检查了8周龄和25月龄小鼠的关节。对于实验模型，我们开发了三种不同的踝关节OA模型：内侧模型，外侧模型和双侧模型，通过切除各自的结构。术后8周通过番红O染色评估OA严重程度，并依次检查内侧模型中的软骨降解。结果：人和小鼠踝关节的解剖学和组织学特征具有可比性。此外，小鼠踝关节比小鼠膝关节更能抵抗随着年龄增长的软骨退化。在内侧模型中，胫距关节受到明显影响，而距下关节退化较少。在外侧模型中，距下关节主要受到影响，而胫距关节的变化较小。在双侧模型中，双侧关节均明显退化。在内侧模型的时间进程中，TdT介导的dUTP缺口末端标记（TUNEL）染色和Adamts 5表达在早期和中期增强，而Mmp 13表达在OA发展过程中逐渐增强。结论：由于人和小鼠踝关节具有可比性，本模型将有助于踝关节OA病理生理学和一般软骨研究的未来。(C)2015国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Prevalence of ankle osteoarthritis (OA) is lower than that of knee OA, however, the molecular mechanisms underlying the difference remain unrevealed. In the present study, we developed mouse ankle OA models for use as tools to investigate pathophysiology of ankle OA and molecular characteristics of ankle cartilage.Design: We anatomically and histologically examined ankle and knee joints of C57BL/6 mice, and compared them with human samples. We examined joints of 8-week-old and 25-month-old mice. For experimental models, we developed three different ankle OA models: a medial model, a lateral model, and a bilateral model, by resection of respective structures. OA severity was evaluated 8 weeks after the surgery by safranin O staining, and cartilage degradation in the medial model was sequentially examined.Results: Anatomical and histological features of human and mouse ankle joints were comparable. Additionally, the mouse ankle joint was more resistant to cartilage degeneration with aging than the mouse knee joint. In the medial model, the tibiotalar joint was markedly affected while the subtalar joint was less degenerated. In the lateral model, the subtalar joint was mainly affected while the tibiotalar joint was less altered. In the bilateral model, both joints were markedly degenerated. In the time course of the medial model, TdT-mediated dUTP nick end labeling (TUNEL) staining and Adamts5 expression were enhanced at early and middle stages, while Mmp13 expression was gradually increased during the OA development.Conclusion: Since human and mouse ankles are comparable, the present models will contribute to ankle OA pathophysiology and general cartilage research in future. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.