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首页> 外文期刊>Osteoarthritis and cartilage >Chondroitin sulfate modulation of matrix and inflammatory gene expression in IL-1beta-stimulated chondrocytes - study in hypoxic alginate bead cultures.
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Chondroitin sulfate modulation of matrix and inflammatory gene expression in IL-1beta-stimulated chondrocytes - study in hypoxic alginate bead cultures.

机译：硫酸软骨素对IL-1β刺激的软骨细胞中基质和炎性基因表达的调节-在低氧海藻酸盐珠培养物中进行研究。

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OBJECTIVE: To determine the effect of avian chondroitin sulfate (CS) on interleukin-1beta (IL-1beta)-induced expression of genes related to catabolic, anabolic and inflammatory aspects in chondrocytes cultured in hypoxic alginate beads. DESIGN: Articular chondrocytes from bovine metacarpal joint were isolated and cultured in alginate beads, using low oxygen atmosphere (5% O(2)). After 1-week exposure to CS (1, 10 and 100mug/ml), they were treated by recIL-1beta (10ng/ml) for 24 or 48h, in the presence of CS. RNA was extracted and used to determine, by quantitative reverse transcription-polymerase chain reaction, the steady-state levels of mRNAs encoding several genes related to anabolic, catabolic and inflammatory aspects. Glycosaminoglycan (GAG) synthesis was also assayed by (35)S-sulfate incorporation. RESULTS: CS decreased IL-1beta-induced expression of matrix metalloproteases-1, -3 and -13 and aggrecanases-1 and -2. It slightly enhanced the aggrecan core protein mRNA and the GAG synthesis. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA levels were found to be reduced by CS treatment. However, no CS-induced decrease of NO was observed in IL-1beta-treated chondrocytes, whereas prostaglandin E(2) production was diminished in correlation with the COX-2 mRNA amounts. Furthermore, CS was capable of counteracting IL-1beta-depressed expression of transforming growth factor-beta (TGF-beta) receptors. CONCLUSIONS: CS can repress expression of genes encoding proteolytic enzymes involved in cartilage degradation. It also inhibits IL-1beta-induced expression of the pro-inflammatory genes iNOS and COX-2 and restores TGF-beta receptors I and II (TGF-betaRI and RII) mRNA levels. These data suggest that CS may exert both chondroprotective and anti-inflammatory limited effects on articular cartilage that could have long-term beneficial action on the osteoarthritic process.
机译：目的：确定硫酸鸟软骨素（CS）对白细胞介素1β（IL-1beta）诱导的缺氧海藻酸盐珠培养的软骨细胞中分解代谢，合成代谢和炎症相关基因表达的影响。设计：分离牛掌骨关节软骨细胞，并在低氧气氛下（5％O（2））在藻酸盐珠中培养。在暴露于CS（1、10和100 ug / ml）中1周后，在存在CS的情况下，将它们通过recIL-1beta（10ng / ml）处理24或48h。提取RNA，并通过定量逆转录-聚合酶链反应用于确定编码与合成代谢，分解代谢和炎症相关的几种基因的mRNA的稳态水平。还通过（35）S-硫酸盐掺入法测定了糖胺聚糖（GAG）的合成。结果：CS降低IL-1β诱导的基质金属蛋白酶-1，-3和-13以及聚集蛋白聚糖酶-1和-2的表达。它稍微增强了聚集蛋白聚糖核心蛋白的mRNA和GAG的合成。发现CS处理可降低一氧化氮合酶（iNOS）和环氧合酶2（COX-2）mRNA的水平。但是，在IL-1beta处理的软骨细胞中未观察到CS诱导的NO减少，而前列腺素E（2）的产生与COX-2 mRNA的量相关。此外，CS能够抵消IL-1beta抑制的转化生长因子-beta（TGF-beta）受体的表达。结论：CS可以抑制涉及软骨降解的蛋白水解酶基因的表达。它还抑制IL-1β诱导的促炎基因iNOS和COX-2的表达，并恢复TGF-β受体I和II（TGF-βRI和RII）的mRNA水平。这些数据表明，CS可能对关节软骨产生软骨保护和抗炎作用，而这些作用可能对骨关节炎过程具有长期有益的作用。

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