Effect of mechanical stress on chondrocytes metabolism

为探讨机械应力诱导软骨降解的机制，采用Flexercell应变仪，观察了周期性张力（CTF）对体外培养软骨细胞代谢的影响。5或15 kPa高频CTF明显抑制DNA、蛋白多糖、胶原和蛋白质的合成。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表达，并增加MMP-9前体和活性的产生。MMPs Inhibitor可抑制蛋白多糖的降解，说明MMPs参与了高频CTF诱导的蛋白多糖的降解，并且随着CTF频率由高到低降低，对蛋白多糖合成的抑制作用减弱。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，表明这种强度的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MMP-8蛋白的产生增加，表明过度和持续的周期性机械应力诱导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.