Messenger-RNA expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, and transcription factors in rheumatic synovial cells under mechanical stimuli.
Messenger-RNA expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, and transcription factors in rheumatic synovial cells under mechanical stimuli.
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DOI：
10.1016/s8756-3282(00)00454-3
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发表时间：
2001-03
期刊：
影响因子：
4.1
通讯作者：
H. B. Sun;H. Yokota
中科院分区：
文献类型：
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作者：
H. B. Sun;H. Yokota
为了阐明机械刺激在类风湿关节炎中的作用，我们测定了两种机械剪切条件以及模拟卸载条件下基质金属蛋白酶（MMP）-1，MMP-3，MMP-13，金属蛋白酶组织抑制剂（TIMP）-1，TIMP-2以及三种转录因子（c-fos，ets-1，ets-2）的mRNA水平。人滑膜细胞培养物（MH 7A和RA 99 -01），来自类风湿性关节炎患者，在机械刺激下生长1小时，并通过逆转录-聚合酶链反应程序测定转录水平。首先，估计为0.1 dyn/cm 2的温和剪切诱导MMP-1、MMP-3、MMP-13和ets-1的mRNA水平持续下降，以及TIMP-1、TIMP-2、c-fos和ets-2的转录水平增加。第二，中间剪切，估计在1.6dyn/cm 2，提高所有MMP，TIMP和三个转录因子的mRNA水平。第三，最低的mRNA水平的c-fos，ets-1，ets-2的控制条件下，分别达到休息，温和的剪切，和模拟卸载。这些在体外的结果支持刺激依赖性的转录调控MMPs，TIMPs和转录因子在细胞培养物中，表明剪切应力在组织降解和预防风湿性关节的潜在作用。
In an effort to elucidate the role of mechanical stimuli in rheumatoid arthritis, we determined mRNA levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, and three transcription factors (c-fos, ets-1, and ets-2) under two mechanical shearing conditions as well as simulated unloading. Human synovial cell cultures (MH7A and RA99-01), derived from rheumatoid arthritis patients, were grown for 1 h under mechanical stimuli and the transcript level was assayed by the reverse transcription-polymerase-chain reaction procedure. First, gentle shearing, estimated at ∼1 dyn/cm2, induced a consistent decrease in mRNA level of MMP-1, MMP-3, MMP-13, and ets-1 and an increase in the transcript level of TIMP-1, TIMP-2, c-fos, and ets-2. Second, intermediate shearing, estimated at ∼6 dyn/cm2, elevated the mRNA level of all MMPs, TIMPs, and the three transcription factors. Third, minimum mRNA level of c-fos, ets-1, and ets-2 was achieved under control conditions at rest, gentle shearing, and simulated unloading, respectively. These in vitro results support a stimulus-dependent transcriptional regulation of MMPs, TIMPs, and transcription factors in cell cultures, suggesting a potential role of shear stress in tissue degradation and prevention in rheumatic joints.