title: Disordered glycometabolism involved in pathogenesis of Kashin-Beck disease, an endemic osteoarthritis in China.
abstract: 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.
authors.affiliation: 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. Electronic address: xj.cy.69@stu.xjtu.edu.cn.
authors.forename: Cuiyan
authors.initials: C
authors.lastname: Wu
authors.affiliation: 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. Electronic address: leirh@mail.xjtu.edu.cn.
authors.forename: Ronghui
authors.initials: R
authors.lastname: Lei
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland. Electronic address: mika.tiainen@uef.fi.
authors.forename: Mika
authors.initials: M
authors.lastname: Tiainen
authors.affiliation: 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. Electronic address: wushixun313@stu.xjtu.edu.cn.
authors.forename: Shixun
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Kashin-Beck Disease, Qinghai Institute for Endemic Disease Control and Prevention, Xining, Qinghai 811602, PR China. Electronic address: wdrr@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: peifuxing@vip.163.com.
authors.forename: Fuxing
authors.initials: F
authors.lastname: Pei
authors.affiliation: 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. Electronic address: guox@mail.xjtu.edu.cn.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
mesh_terms: D000368:Aged; D053674:Aggrecans / Q000378:metabolism; D016022:Case-Control Studies; D002681:China; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D057767:Kashin-Beck Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D008875:Middle Aged; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D024043:Collagen Type II; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006003:Glycogen; D005947:Glucose
keywords: Chondrocyte; Glycometabolism; Kashin–Beck disease; Metabolomics; Serum