期刊
OSTEOARTHRITIS AND CARTILAGE
卷 23, 期 9, 页码 1513-1522出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2015.04.026
关键词
Osteoarthritis; Glucose; Diabetes mellitus; Metabolic osteoarthritis; Oxidative stress
资金
- French state Transimmunom funds
- ANR within the Investissements d'Avenir program [ANR-11-IDEX-0004-02]
- French Ministere de l'Education Nationale, de la Recherche et de la Technologie
- Annee Recherche program (AP-HP, Paris, France)
Objective: To examine the relationship between osteoarthritis (OA) and type 2 diabetes mellitus (DM). Methods: OA cartilage from DM and non-DM patients undergoing knee replacement were stimulated by IL-1 beta for 24 h and release of interleukin-6 (IL-6) and prostaglandin E-2 (PGE(2)) was measured. Primary cultured murine chondrocytes were stimulated for 24 and 72 h with or without IL-1 beta (5 ng/mL) under normal-glucose (5.5 mM) or high-glucose (25 mM) conditions. The expression and release of proinflammatory mediators (IL-6, cyclooxygenase 2 [COX2]/PGE(2)) were analyzed by quantitative RT-PCR and ELISA/EIA. Glucose uptake was assessed with (C-14)-2-deoxyglucose. Reactive oxygen species (ROS) and nitric oxide (NO) production were measured. To analyze the mechanism of IL-1 beta-induced inflammation, cells were pretreated or treated with inhibitors of glucose transport (cytochalasin B), the polyol pathway (epalrestat), mitochondrial oxidative stress (MitoTEMPO) or nitric oxide synthase (L-NAME). Results: With IL-1 beta stimulation, IL-6 and PGE2 release was greater in human DM than non-DM OA cartilage (2.7- and 3-fold, respectively) (P < 0.05). In vitro, with IL-1 beta stimulation, IL-6 and COX2 mRNA expression, IL-6 and PGE2 release, and ROS and NO production were greater under high-than normal-glucose conditions in cultured chondrocytes. IL-1 beta-increased IL-6 release was reduced with cytochalasin B, epalrestat, L-NAME or MitoTEMPO treatment (-45%, -62%, -38% and -40%, respectively). Conclusion: OA cartilages from DM patients showed increased responsiveness to IL-1 beta-induced inflammation. Accordingly, high glucose enhanced IL-1 beta-induced inflammation in cultured chondrocytes via oxidative stress and the polyol pathway. High glucose and diabetes may thus participate in the increased inflammation in OA. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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