The effect of IL-1α on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in osteoblastic ROS 17/2.8 cells
The effect of IL-1α on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in osteoblastic ROS 17/2.8 cells
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DOI：
10.1016/j.lfs.2005.08.036
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发表时间：
2006-03-20
期刊：
影响因子：
6.1
通讯作者：
Maeno, M
中科院分区：
文献类型：
--
作者：
Fujisaki, K;Tanabe, N;Maeno, M
白细胞介素-1 （IL-1）在改变骨基质转换中起关键作用。这种转换由基质金属蛋白酶（MMPs）、基质金属蛋白酶的组织抑制剂（TIMPs）和纤溶酶原激活系统（包括组织型纤溶酶原激活剂（tPA）、尿激酶型纤溶酶原激活剂（uPA）和纤溶酶原激活剂抑制剂1型（PAI-1））调节。在本研究中，我们检测了IL-1 α对来自大鼠骨肉瘤细胞系ROS 17/2.8的成骨细胞中MMPs、TIMPs、tPA、uPA和PAI-1基因表达的影响。细胞在含有10%胎牛血清和0或100 U/ml IL-1 α的α -minimum基本培养基中培养14天。通过实时RT-PCR测定mRNA水平和ELISA测定蛋白水平，估计MMPs、TIMPs、uPA、tPA和PAI-1的表达水平。在IL-1 α培养中，MMP-1、-2 -3、-13和-14的表达量在培养第14天就超过了对照，并且从增殖到培养后期，MMPs的表达量明显增加。TIMP-1、-2和-3的表达水平从培养初期到增殖阶段均有所增加。tPA的表达在培养增殖阶段显著增加，uPA的表达在整个培养过程中均呈上升趋势，从增殖阶段到培养后期显著增加。相比之下，在1L-1 α存在的情况下，PAI-1的表达在第14天下降。这些结果表明，IL-1 α通过增加成骨细胞的MMPs、tPA和uPA的产生，减少成骨细胞的PAI-1的产生，从而刺激骨基质的更新，并使更新倾向于分辨率。(c) 2005爱思唯尔公司版权所有。
Interleukin-1 (IL-1) plays key roles in altering bone matrix turnover. This turnover is regulated by matrix metalloproteinases (MMPs), tissue inhibitor of matrix metalloproteinases (TIMPs), and the plasminogen activation system, including tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and plasminogen activator inhibitor type-1 (PAI-1). In this study, we examined the effect of IL-1 alpha on the expression of the MMPs, TIMPs, tPA, uPA, and PAI-1 genes in osteoblasts derived from the rat osteosarcoma cell line ROS 17/2.8. The cells were cultured in alpha-minimum essential medium containing 10% fetal bovine serum with 0 or 100 U/ml of IL-1 alpha for up to 14 days. The levels of MMPs, TIMPs, uPA, tPA, and PAI-1 expression were estimated by determining the mRNA levels using real-time RT-PCR and by determining protein levels using ELISA. In IL-1 alpha cultures, the expression levels of MMP-1, -2 -3, -13, and -14 exceeded that of the control through day 14 of culture, and the expression of MMPs increased markedly from the proliferative to the later stages of culture. The TIMP-1, -2, and -3 expression levels increased from the initial to the proliferative stages of culture. The expression of tPA increased greatly during the proliferative stage of culture, and uPA expression increased throughout the culture period, increasing markedly from the proliferative to the later stages of culture. In contrast, PAI-1 expression decreased in the presence of 1L-1 alpha through day 14. These results suggest that IL-1 alpha stimulate bone matrix turnover by increasing MMPs, tPA, and uPA production and decreasing PAI-1 production by osteoblasts, and incline the turnover to the resolution. (c) 2005 Elsevier Inc. All rights reserved.