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 II 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 (nonpassaged) 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.
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 II 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 (nonpassaged) 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.
Authors: Stefan Toegel; Shengqian Q Wu; Miguel Otero; Mary B Goldring; Pimporn Leelapornpisid; Catharina Chiari; Alexander Kolb; Frank M Unger; Reinhard Windhager; Helmut Viernstein Journal: Genes Nutr Date: 2011-08-18 Impact factor: 5.523
Authors: Amy M Silverstein; Aaron M Stoker; Gerard A Ateshian; J Chloe Bulinski; James L Cook; Clark T Hung Journal: J Orthop Res Date: 2016-05-29 Impact factor: 3.494
Authors: Michael Kreinest; Gregor Reisig; Philipp Ströbel; Stefan Fickert; Joachim Brade; Gunther Wennemuth; Peter Lipp; Markus L Schwarz Journal: Comp Med Date: 2016-02 Impact factor: 0.982