Involvement of the oxidized low-density lipoprotein/lectin-like oxidized low-density lipoprotein receptor-1 system to joint cartilage degeneration

本研究的目的是使用LOX-1敲除（KO）小鼠来证明ox-LDL/LOX-1系统参与体内关节软骨退变。采用非手术方法建立小鼠膝关节骨关节炎模型，通过改变强迫跑次数和跑时间来控制跑台上的强迫跑来施加机械负荷。变性评分的变化以时间和剂量依赖性方式显著增加。然而，与野生型小鼠相比，LOX-1 KO在该OA模型中在2周的强迫跑步后没有显示出显著的保护作用。然而，长期观察（1年和1.5年）的KO小鼠和野生型小鼠在笼中饲养的传统揭示了软骨退化的显着差异。此外，LOX-1 KO抑制酵母多糖诱导的关节炎中的滑膜炎和软骨变性。这些结果表明ox-LDL/LOX-1系统参与了体内关节软骨的退变。结论ox-LDL/LOX-1系统不仅在动脉粥样硬化的内皮功能障碍中起作用，而且在软骨退变中也起作用。

Purpose of this study is to demonstrate involvement of the ox-LDL/LOX-1 system to joint cartilage degeneration in vivo using LOX-1 knockout (KO) mouse. To develop a nonsurgical murine knee osteoarthritis model, mechanical load is applied by forced running on a treadmill, which was controlled by changing number of forced running periods and running time. Changes in the degeneration score increased significantly in a time- and dose-dependent manner. However, LOX-1 KO did not show significant protective effects in this OA model after 2-week forced running, compared with wild type mice. While, long-term observation (1 and 1.5 year) of the KO mice and wild type mice bred conventionally in cages revealed significant difference in cartilage degeneration. Furthermore, LOX-1 KO suppressed synovitis and cartilage degeneration in zymosan induced arthritis. These results indicate that the ox-LDL/LOX-1 system is involved to joint cartilage degeneration in vivo. In conclusion, the ox-LDL/LOX-1 system may play some role not only in endothelial dysfunction of atherosclerosis but also in cartilage degeneration.