Neil Kirsten M, Orth Michael W, Coussens Paul M, Chan Pooi-See, Caron John P
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA.
Am J Vet Res. 2005 Nov;66(11):1861-9. doi: 10.2460/ajvr.2005.66.1861.
To determine whether glucosamine and chondroitin sulfate (CS) at concentrations approximating those achieved in plasma by oral administration would influence gene expression of selected mediators of osteoarthritis in cytokine-stimulated equine articular chondrocytes.
Samples of grossly normal articular cartilage obtained from the metacarpophalangeal joint of 13 horses.
Equine chondrocytes in pellet culture were stimulated with a subsaturating dose of recombinant equine interleukin (reIL)-1beta. Effects of prior incubation with glucosamine (2.5 to 10.0 microg/mL) and CS (5.0 to 50.0 microg/mL) on gene expression of matrix metalloproteinase (MMP)-1, -2, -3, -9, and -13; aggrecanase 1 and 2; inducible nitric oxide synthase (iNOS); cyclooxygenase (COX)-2; nuclear factor kappaB; and c-Jun-N-terminal kinase (JNK) were assessed by use of a quantitative real-time polymerase chain reaction assay.
Glucosamine at a concentration of 10 microg/mL significantly reduced reIL-1beta-induced mRNA expression of MMP-13, aggrecanase 1, and JNK. Reductions in cytokine-induced expression were also observed for iNOS and COX-2. Chondroitin sulfate had no effect on gene expression at the concentrations tested.
Concentrations of glucosamine similar to those achieved in plasma after oral administration in horses exerted pretranslational regulation of some mediators of osteoarthritis, an effect that may contribute to the cartilage-sparing properties of this aminomonosaccharide. Analysis of results of this study indicated that the influence of CS on pretranslational regulation of these selected genes is limited or lacking.
确定口服给药后血浆中达到的浓度的氨基葡萄糖和硫酸软骨素(CS)是否会影响细胞因子刺激的马关节软骨细胞中骨关节炎选定介质的基因表达。
从13匹马的掌指关节获取的大体正常关节软骨样本。
用亚饱和剂量的重组马白细胞介素(reIL)-1β刺激颗粒培养中的马软骨细胞。通过定量实时聚合酶链反应测定评估预先用氨基葡萄糖(2.5至10.0μg/mL)和CS(5.0至50.0μg/mL)孵育对基质金属蛋白酶(MMP)-1、-2、-3、-9和-13;聚集蛋白聚糖酶1和2;诱导型一氧化氮合酶(iNOS);环氧化酶(COX)-2;核因子κB;以及c-Jun氨基末端激酶(JNK)基因表达的影响。
浓度为10μg/mL的氨基葡萄糖显著降低了reIL-1β诱导的MMP-13、聚集蛋白聚糖酶1和JNK的mRNA表达。还观察到iNOS和COX-2的细胞因子诱导表达降低。在所测试的浓度下,硫酸软骨素对基因表达没有影响。
与马口服给药后血浆中达到的浓度相似的氨基葡萄糖浓度对骨关节炎的一些介质发挥了翻译前调节作用,这种作用可能有助于这种氨基单糖的软骨保护特性。对本研究结果的分析表明,CS对这些选定基因的翻译前调节的影响有限或不存在。