Characterization of diabetic osteoarthritic cartilage and role of high glucose environment on chondrocyte activation: toward pathophysiological delineation of diabetes mellitus-related osteoarthritis

Summary 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-1β for 24 h and release of interleukin-6 (IL-6) and prostaglandin E2 (PGE2 ) was measured. Primary cultured murine chondrocytes were stimulated for 24 and 72 h with or without IL-1β (5 ng/mL) under normal-glucose (5.5 mM) or high-glucose (25 mM) conditions. The expression and release of pro-inflammatory mediators (IL-6, cyclooxygenase 2 [COX2]/PGE2 ) were analyzed by quantitative RT-PCR and ELISA/EIA. Glucose uptake was assessed with (14 C)-2-deoxyglucose. Reactive oxygen species (ROS) and nitric oxide (NO) production were measured. To analyze the mechanism of IL-1β-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-1β stimulation, IL-6 and PGE2 release was greater in human DM than non-DM OA cartilage (2.7- and 3-fold, respectively) ( P