Freshly isolated osteoarthritic chondrocytes are catabolically more active than normal chondrocytes, but less responsive to catabolic stimulation with interleukin-1β
Freshly isolated osteoarthritic chondrocytes are catabolically more active than normal chondrocytes, but less responsive to catabolic stimulation with interleukin-1β
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DOI：
10.1002/art.20725
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发表时间：
2005-01-01
影响因子：
--
通讯作者：
Aigner, T
中科院分区：
文献类型：
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作者：
Fan, ZY;Bau, B;Aigner, T
客观的。白细胞介素-1β (IL-1beta) 是软骨破坏过程中一种潜在的重要细胞因子。本研究的目的是探讨低浓度和高浓度的IL-1β对关节蛋白的合成代谢基因（H型胶原蛋白、聚集蛋白聚糖）、分解代谢基因（基质金属蛋白酶1 [MMP-1]、MMP-2、MMP-3、MMP-13和ADAMTS-4）和细胞因子（IL-1β、IL-6和白血病抑制因子[LIF]）的表达水平是否有不同的影响。软骨细胞（正常和骨关节炎）。确定正常软骨细胞和骨关节炎软骨细胞之间的反应性是否存在差异也是本研究的目标。方法。用 0.01 ng、0.1 ng、1 ng 和 10 ng/ml IL-1beta 刺激后，通过实时聚合酶链反应检测分离的（未传代）软骨细胞（正常 [n = 6]；骨关节炎 [n = 7]）的基因表达水平。结果。在正常成人关节软骨细胞中，聚集蛋白聚糖和 II 型胶原基因的表达均显着下调，而基质降解蛋白酶（MMP-2 除外）以及所研究的细胞因子均被 IL-1β 以剂量依赖性方式诱导。 IL-6 和 LIF 的调节最强。骨关节炎软骨细胞的分解代谢酶和介质水平显着升高，但对 IL-1β 的进一步刺激反应较差。结论。我们的研究证实，IL-1β 活性严重依赖于所应用的浓度和所刺激细胞的反应性。晚期骨关节炎软骨细胞的反应性似乎显着降低。然而，这些细胞显示出分解代谢酶和介质的高基本表达水平。因此，我们的数据是否表明骨关节炎软骨细胞本身对 IL-1β 没有反应，或者在疾病过程中已经受到如此强烈的刺激（例如，通过 IL-1）以至于它们对进一步的刺激产生抵抗力，这仍然是一个悬而未决的问题。
Objective. Interleukin-1beta (IL-1beta) is one potentially important cytokine during cartilage destruction. The aim of this study was to investigate whether there are different effects of low and high concentrations of IL-1beta on the expression level of anabolic genes (type H collagen, aggrecan), catabolic genes (matrix metalloproteinase 1 [MMP-1], MMP-2, MMP-3, MMP-13, and ADAMTS-4), and cytokines (IL-1beta, IL-6, and leukemia inhibitory factor [LIF]) by articular chondrocytes (normal and osteoarthritic). Determination of whether there was a difference in reactivity between normal and osteoarthritic chondrocytes was also a goal of this study.Methods. Gene expression levels were detected by real-time polymerase chain reaction from isolated (non-passaged) chondrocytes (normal [n = 6]; osteoarthritic [n = 7]) after stimulation with 0.01 ng, 0.1 ng, 1 ng, and 10 ng/ml IL-1beta.Results. In normal adult articular chondrocytes the expression of both aggrecan and type II collagen genes was significantly down-regulated, whereas matrix-degrading proteases (except MMP-2), as well as the investigated cytokines, were induced by IL-1beta in a dose-dependent manner. The strongest regulation was found for IL-6 and LIF. Osteoarthritic chondrocytes showed strongly increased levels of catabolic enzymes and mediators, but were less responsive to further stimulation with IL-1beta.Conclusion. Our study confirms that IL-1beta activity is critically dependent on both the applied concentration and the reactivity of the cells stimulated. The responsiveness appears to be significantly reduced in late-stage osteoarthritic chondrocytes. However, these cells show high basic expression levels of catabolic enzymes and mediators. Thus, it remains open whether our data indicate that osteoarthritic chondrocytes are per se not responsive to IL-1beta or are already so strongly stimulated (e.g., by IL-1) during the disease process that they are refractory to further stimulation.