Wolf Amela, Raiss Ruth X, Steinmeyer Jürgen
Department of Pharmacology and Toxicology, Rheinische Friedrich-Wilhelms-Universität Bonn, Reuterstrasse 2b, D-53113 Bonn, Germany.
J Orthop Res. 2003 Nov;21(6):1081-9. doi: 10.1016/S0736-0266(03)00064-0.
Chondrocytes within articular cartilage experience complete unloading between loading cycles and in so doing utilize mechanical signals to regulate their own metabolic activities. A strongly elevated fibronectin content is an early feature in osteoarthritis and appears to be related to increases in both the synthesis and retention of this glycoprotein. The objectives of this study were to investigate systematically whether the frequency of intermittently applied cyclic mechanical loading of cartilage explants alters the biosynthesis and retention of fibronectin, and to assess whether it is possible to induce in vitro osteoarthritic-like changes of this metabolic parameter by mechanical means over a period of 6 days. Cartilage plugs consisting of viability-checked chondrocytes were exposed to sinusoidal cyclic compressive pressure alterations of 0.1, 0.5 or 1.0 Hz frequency with a peak stress of 0.5 MPa for a period of 5, 10 or 20 s, followed by an unloading period of 10, 100 or 1000 s, and compared to unloaded reference plugs from the same joint and topographic origin. The incorporation of radioactive precursor into fibronectin during the last 18 h, the content of fibronectin, and the viability of chondrocytes were determined. Our data revealed that (a) the fibronectin synthesis was selectively, but non-linearly affected by the frequency of intermittent loads applied (as defined by the frequency of the applied force, the duration of the loading cycle and the duration of the force-free period between each loading cycle), and that (b) the retention of endogenous fibronectin and proteins within loaded cartilage explants is strongly elevated. These data support our hypothesis that the mechanical factor "frequency of intermittent loading" seems to be the crucial mechanical parameter controlling the metabolism of chondrocytes. The effect of the frequency of intermittent loading cannot be described by a simple statistical correlation, so that no specific predictions are possible. However, our results imply that distinct loading protocols have been established that can induce alterations of the fibronectin metabolism similar to those observed in human and animal osteoarthritis.
关节软骨内的软骨细胞在加载周期之间经历完全卸载，并利用机械信号调节自身的代谢活动。骨关节炎的一个早期特征是纤连蛋白含量显著升高，这似乎与这种糖蛋白的合成和保留增加有关。本研究的目的是系统地研究软骨外植体间歇性施加循环机械负荷的频率是否会改变纤连蛋白的生物合成和保留，并评估是否有可能在6天的时间内通过机械手段在体外诱导该代谢参数出现类似骨关节炎的变化。由经过活力检查的软骨细胞组成的软骨栓暴露于频率为0.1、0.5或1.0Hz、峰值应力为0.5MPa的正弦循环压缩压力变化下5、10或20秒，随后是10、100或1000秒的卸载期，并与来自同一关节和地形来源的未加载参考栓进行比较。测定了在最后18小时内放射性前体掺入纤连蛋白的情况、纤连蛋白的含量以及软骨细胞的活力。我们的数据显示：（a）纤连蛋白的合成受到间歇性负荷频率的选择性但非线性影响（由施加力的频率、加载周期的持续时间以及每个加载周期之间无作用力期的持续时间定义），并且（b）加载的软骨外植体内内源性纤连蛋白和蛋白质的保留显著增加。这些数据支持了我们的假设，即机械因素“间歇性负荷频率”似乎是控制软骨细胞代谢的关键机械参数。间歇性负荷频率的影响无法用简单的统计相关性来描述，因此无法进行具体预测。然而，我们的结果表明，已经建立了不同的加载方案，这些方案可以诱导纤连蛋白代谢的改变，类似于在人类和动物骨关节炎中观察到的情况。
