School of Public Health, Health Science Centre of Xi׳an Jiaotong University, No. 76 Yanta West Road, Xi׳an, Shaanxi 710061, PR China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, PR China; Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi׳an, Shaanxi 710061, PR China.
School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Exp Cell Res. 2014 Aug 15;326(2):240-50. doi: 10.1016/j.yexcr.2014.04.019. Epub 2014 May 2.
Kashin-Beck disease (KBD) is a chronic endemic osteoarthritis in China. Previous studies have suggested a role of metabolic dysfunction in causation of this disease. In this investigation, the metabolomics approach and cell experiments were used to discover the metabolic changes and their effects on KBD chondrocytes. Nuclear magnetic resonance ((1)H NMR) spectroscopy was used to examine serum samples from both the KBD patients and normal controls. The pattern recognition multivariate analysis (OSC-PLS) and quantitative analysis (QMTLS iterator) revealed altered glycometabolism in KBD, with increased glucose and decreased lactate and citrate levels. IPA biological analysis showed the centric location of glucose in the metabolic network. Massive glycogen deposits in chondrocytes and increased uptake of glucose by chondrocytes further confirmed disordered glycometabolism in KBD. An in vitro study showed the effects of disordered glycometabolism in chondrocytes. When chondrocytes were treated with high glucose, expression of type II collagen and aggrecan were decreased, while TNF-α expression, the level of cellular reactive oxygen species and cell apoptosis rates all were increased. Therefore, our results demonstrated that disordered glycometabolism in patients with KBD was linked to the damage of chondrocytes. This may provide a new basis for understanding the pathogenesis of KBD.
大骨节病（KBD）是中国的一种慢性地方性骨关节炎。先前的研究表明代谢功能障碍在该病的发病机制中起作用。在这项研究中，我们采用代谢组学方法和细胞实验来发现代谢变化及其对 KBD 软骨细胞的影响。使用核磁共振（1H NMR）波谱分析了来自 KBD 患者和正常对照者的血清样本。通过模式识别多变量分析（OSC-PLS）和定量分析（QMTLS 迭代器）揭示了 KBD 中的糖代谢变化，葡萄糖升高，乳酸和柠檬酸水平降低。IPA 生物分析显示葡萄糖在代谢网络中的中心位置。软骨细胞中大量的糖原沉积和软骨细胞对葡萄糖摄取的增加进一步证实了 KBD 中的糖代谢紊乱。体外研究显示了软骨细胞中糖代谢紊乱的影响。当软骨细胞用高葡萄糖处理时，II 型胶原和聚集蛋白聚糖的表达减少，而 TNF-α 表达、细胞活性氧水平和细胞凋亡率均增加。因此，我们的结果表明 KBD 患者的糖代谢紊乱与软骨细胞的损伤有关。这可能为理解 KBD 的发病机制提供新的依据。
