Sauerland K, Raiss R X, Steinmeyer J
Department of Pharmacology and Toxicology, Rheinische Friedrich-Wilhelms-Universität Bonn, Reuterstrasse 2b, D-53113 Bonn, Germany.
Osteoarthritis Cartilage. 2003 May;11(5):343-50. doi: 10.1016/s1063-4584(03)00007-4.
This study was designed to systematically determine whether and to what extent the frequency of intermittent loading modulates the biosynthesis and release of proteoglycans (PGs), and to assess chondrocyte viability within mature bovine articular cartilage explants exposed to different loading patterns.
Cultured full-thickness cartilage explants from the weight-bearing area of healthy bovine fetlock joints were exposed to intermittently applied, uniaxial cyclic loads by introducing a sinusoidal waveform of 0.1, 0.5 or 1.0Hz, frequency and a peak stress of 0.5MPa for a period of 6 days. The cyclic loads were applied for 5, 10 or 20s followed by a period of unloading lasting 10, 100 or 1000s. The incorporation of radiolabeled sulfate into glycosaminoglycans (GAGs) during the final 18h, the content of GAGs and DNA, the deformation of loaded explants as well as the viability of chondrocytes within the different zones of explants were determined.
PG synthesis and loss of endogenous PGs were non-linearly and independently regulated by the frequency of the chosen intermittent load, whereas the release of newly synthesized PGs remained unaffected. The viability of chondrocytes within the superficial zone decreased drastically under intermittent loading in a manner independent of the frequency applied.
Our results confirm the hypothesis that the frequency of intermittent loading is an important mechanical factor controlling the metabolic activities of chondrocytes. They also implicate that an initially healthy cartilage explant can be mechanically manipulated to generate an in vitro model of degenerative, osteoarthritic-like cartilage.
本研究旨在系统地确定间歇性加载的频率是否以及在何种程度上调节蛋白聚糖（PGs）的生物合成和释放，并评估暴露于不同加载模式下的成熟牛关节软骨外植体中软骨细胞的活力。
从健康牛跗关节负重区培养的全层软骨外植体，通过引入频率为0.1、0.5或1.0Hz的正弦波形和0.5MPa的峰值应力，进行间歇性单轴循环加载，持续6天。循环加载5、10或20秒，随后是10、100或1000秒的卸载期。测定在最后18小时内放射性标记硫酸盐掺入糖胺聚糖（GAGs）的情况、GAGs和DNA的含量、加载外植体的变形以及外植体不同区域内软骨细胞的活力。
PG的合成和内源性PG的损失由所选间歇性加载的频率非线性且独立地调节，而新合成PG的释放不受影响。在间歇性加载下，表层区域软骨细胞的活力以与施加频率无关的方式急剧下降。
我们的结果证实了间歇性加载频率是控制软骨细胞代谢活动的重要机械因素这一假设。它们还表明，最初健康的软骨外植体可以通过机械操作来生成退行性骨关节炎样软骨的体外模型。
