Sun Hui Bin, Nalim Razi, Yokota Hiroki
Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202, USA.
Connect Tissue Res. 2003;44(1):42-9.
Matrix metalloproteinases (MMPs) are known to play a critical role in tissue disintegration, and an elevated level of MMPs is observed in synovium and synovial fluid of joints with rheumatoid arthritis. During joint movement, synovial tissue receives various mechanical stimuli, but effects of mechanical challenges on regulation of MMPs in rheumatic synovium are poorly understood. Focusing on cellular responses to oscillatory fluid shear in human synovial cells, we determined the expression of MMP-1 and MMP-13 by polymerase chain reaction and immunoblotting as well as proteolytic activities of total MMPs by a fibril degradation assay and zymography. The results revealed that approximately 0.5 dyn/cm2 oscillatory shear at 1 Hz not only reduced an mRNA level and a protein level of MMP-1 and MMP-13, but it also decreased collagenase and gelatinase activities of total MMPs. Furthermore, the induction of the MMP expression and activities by interleukin-1 was suppressed by the oscillatory shear. Interestingly, the oscillatory shear upregulated the mRNA expression of TIMP-1 and TIMP-2. Our results support a potential role of oscillatory shear in regulating expression and activities of MMPs in the presence and the absence of proinflammatory cytokine.
基质金属蛋白酶（MMPs）在组织分解中起关键作用，在类风湿性关节炎患者的关节滑膜和滑液中观察到MMPs水平升高。在关节运动过程中，滑膜组织会受到各种机械刺激，但机械刺激对风湿性滑膜中MMPs调节的影响尚不清楚。我们聚焦于人类滑膜细胞对振荡性流体剪切力的细胞反应，通过聚合酶链反应和免疫印迹法测定MMP-1和MMP-13的表达，并通过原纤维降解试验和酶谱法测定总MMPs的蛋白水解活性。结果显示，1Hz频率下约0.5达因/平方厘米的振荡剪切力不仅降低了MMP-1和MMP-13的mRNA水平和蛋白水平，还降低了总MMPs的胶原酶和明胶酶活性。此外，振荡剪切力抑制了白细胞介素-1对MMP表达和活性的诱导作用。有趣的是，振荡剪切力上调了TIMP-1和TIMP-2的mRNA表达。我们的结果支持了振荡剪切力在存在和不存在促炎细胞因子的情况下对MMPs表达和活性的调节作用。
