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Title: Disordered glycometabolism involved in pathogenesis of Kashin–Beck disease, an endemic osteoarthritis in China

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 ({sup 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. - Highlights:more » • Disordered glycometabolism in KBD was demonstrated by combining serum metabolomics and chondrocyte studies. • Glucose and TNF-α were key molecules linked to altered metabolism and inflammation in the pathophysiology of KBD. • The glycometabolism disorder was linked to expression of type II collagen and aggrecan, ROS and apoptosis of KBD chondrocytes.« less
Authors:
 [1] ;  [2] ;  [2] ;  [1] ;  [2] ;  [2] ;  [3] ;  [1] ;  [2] ;  [2] ;  [4] ;  [5] ;  [1] ;  [2] ;  [2]
  1. School of Public Health, Health Science Centre of Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi 710061 (China)
  2. (China)
  3. School of Pharmacy, University of Eastern Finland, Kuopio (Finland)
  4. Department of Kashin–Beck Disease, Qinghai Institute for Endemic Disease Control and Prevention, Xining, Qinghai 811602 (China)
  5. Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China)
Publication Date:
OSTI Identifier:
22416919
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 326; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; COLLAGEN; DISEASES; GLUCOSE; GLYCOGEN; HYDROGEN 1; IN VITRO; INFLAMMATION; LACTATES; METABOLISM; MULTIVARIATE ANALYSIS; NUCLEAR MAGNETIC RESONANCE; PATHOGENESIS; PATTERN RECOGNITION; TRANSMISSION ELECTRON MICROSCOPY