Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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 (14C)-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<0.05). In vitro, with IL-1β 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-1β–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-1β–induced inflammation. Accordingly, high glucose enhanced IL-1β–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.
Document type :
Journal articles
Complete list of metadatas

https://hal.sorbonne-universite.fr/hal-01153393
Contributor : Administrateur Hal-Upmc <>
Submitted on : Tuesday, May 19, 2015 - 5:16:03 PM
Last modification on : Thursday, August 20, 2020 - 3:05:40 AM
Long-term archiving on: : Thursday, April 20, 2017 - 3:31:32 AM

File

Laiguillon_Characterization_of...
Files produced by the author(s)

Identifiers

Citation

Marie-Charlotte Laiguillon, Alice Courties, Xavier Houard, Martine Auclair, Alain Sautet, et al.. Characterization of diabetic osteoarthritic cartilage and role of high glucose environment on chondrocyte activation: toward pathophysiological delineation of diabetes mellitus-related osteoarthritis. Osteoarthritis and Cartilage, Elsevier, 2015, 23 (9), pp.1513-1522. ⟨10.1016/j.joca.2015.04.026⟩. ⟨hal-01153393⟩

Share

Metrics

Record views

289

Files downloads

368