Effect of mechanical stress on chondrocytes metabolism

为了阐明机械应力诱导软骨降解的机制，我们研究了循环张力（CTF）对培养软骨细胞代谢的影响，利用Flexercell应变单元将软骨细胞暴露在CTF下。5或15 kPa的高频CTF显著抑制了DNA、蛋白聚糖、胶原蛋白和蛋白质的合成。15 kPa高频CTF诱导白细胞介素-1 （IL-1）、基质金属蛋白酶(MMP)-2和-9 mRNA的表达，增加了MMP -9的前体和活性。MMP抑制剂抑制了蛋白多糖的降解，表明MMP参与了高频CTF诱导蛋白多糖的降解。此外，将CTF的频率从高降低到低降低了对蛋白多糖合成的抑制作用。这些发现表明CTF频率是软骨细胞代谢的关键决定因素之一。低强度的CTF，无论是高频率还是低频率，都没有引起软骨降解因子的基因表达，说明这种强度的CTF只引起软骨基质的微小变化。高强度和高频率的CTF引起IL-1和MMP-9的基因表达，随后MMP-2和-8蛋白的产生增加，表明过度和持续的循环机械应力诱导了IL-1和MMP-9的产生，导致软骨降解。

To clarify the mechanism of cartilage degradation induced by mechanical stress, we investigated the influence of cyclic tension force (CTF) on the metabolism of cultured chondrocytes, The chondrocytes were exposed to CTF by using Flexercell strain unit. Five or 15 kPa of high frequency CTF significantly inhibited the syntheses of DNA, proteoglycan, collagen and protein. Fifteen kPa of high frequency CTF induced the expression of interleukin-1 (IL-1), matrix metalloproteinase (MMP)-2 and -9 mRNA, and increased the production of pro-and active-Mmp-9. the degradation of proteoglycan was inhibited by MMP Inhibitor, indicating that MMPs are involved in the degradation of proteoglycan induced by high frequency CTF.Moreover reducing the frequency of CTF from high to low decreased the inhibition of proteoglycan synthesis. These findings suggest that the CTF frequency is one of the key determinants of the chondrocyte metabolism. Low magnitude CTF, whether high or low frequency, did not cause the gene expression of cartilage degradation factors, suggesting that this magnitude of CTF causes only minor change of cartilage matrix. High magnitude and frequency CTF caused the gene expression of IL-1 and MMP-9, followed by increases in the production of MMP-2 and -8 protein suggest that excessive and continuous cyclic mechanical stress induces the production of IL-1 and MMP-9, resulting in cartilage degradation.