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首页> 外文期刊>Cytokine >IL-1beta, but not BMP-7 leads to a dramatic change in the gene expression pattern of human adult articular chondrocytes-Portraying the gene expression pattern in two donors.
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IL-1beta, but not BMP-7 leads to a dramatic change in the gene expression pattern of human adult articular chondrocytes-Portraying the gene expression pattern in two donors.

机译：IL-1beta而非BMP-7导致人类成年关节软骨细胞的基因表达模式发生巨大变化-描绘了两个供体中的基因表达模式。

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Anabolic and catabolic cytokines and growth factors such as BMP-7 and IL-1beta play a central role in controlling the balance between degradation and repair of normal and (osteo)arthritic articular cartilage matrix. In this report, we investigated the response of articular chondrocytes to these factors IL-1beta and BMP-7 in terms of changes in gene expression levels. Large scale analysis was performed on primary human adult articular chondrocytes isolated from two human, independent donors cultured in alginate beads (non-stimulated and stimulated with IL-1beta and BMP-7 for 48h) using Affymetrix gene chips (oligo-arrays). Biostatistical and bioinformatic evaluation of gene expression pattern was performed using the Resolver software (Rosetta). Part of the results were confirmed using real-time PCR. IL-1beta modulated significantly 909 out of 3459 genes detectable, whereas BMP-7 influenced only 36 out of 3440. BMP-7 induced mainly anabolic activation of chondrocytes including classical target genes suchas collagen type II and aggrecan, while IL-1beta, both, significantly modulated the gene expression levels of numerous genes; namely, IL-1beta down-regulated the expression of anabolic genes and induced catabolic genes and mediators. Our data indicate that BMP-7 has only a limited effect on differentiated cells, whereas IL-1beta causes a dramatic change in gene expression pattern, i.e. induced or repressed much more genes. This presumably reflects the fact that BMP-7 signaling is effected via one pathway only (i.e. Smad-pathway) whereas IL-1beta is able to signal via a broad variety of intracellular signaling cascades involving the JNK, p38, NFkB and Erk pathways and even influencing BMP signaling.
机译：合成代谢和分解代谢细胞因子以及生长因子（例如BMP-7和IL-1beta）在控制正常和（骨）关节炎软骨基质的降解与修复之间的平衡中起着核心作用。在此报告中，我们研究了基因表达水平变化对关节软骨细胞对这些因子IL-1beta和BMP-7的反应。使用Affymetrix基因芯片（寡核苷酸阵列），对分离自在藻酸盐珠（未用IL-1beta和BMP-7刺激并刺激48h）中培养的两个人独立供体的原代人成年软骨细胞进行了大规模分析。使用Resolver软件（Rosetta）进行基因表达模式的生物统计学和生物信息学评估。使用实时PCR证实了部分结果。 IL-1beta显着调节了3459个基因中的909个，而BMP-7仅影响了3440个基因中的36个。BMP-7主要诱导软骨细胞的合成代谢激活，包括经典的目标基因，例如II型胶原和蛋白聚糖，而IL-1beta都可以。显着调节众多基因的基因表达水平;即，IL-1β下调合成代谢基因的表达，并诱导分解代谢基因和介体的表达。我们的数据表明BMP-7对分化的细胞仅具有有限的作用，而IL-1β引起基因表达模式的急剧变化，即诱导或抑制了更多的基因。这大概反映了一个事实，即BMP-7信号传导仅通过一种途径（即Smad途径）实现，而IL-1beta能够通过涉及JNK，p38，NFkB和Erk途径甚至其他途径的多种细胞内信号传导级联进行信号传导影响BMP信号。

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