Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1ß or TNF-a

Inflammation, which is mainly sustained by pro-inflammatory cytokines such as IL-1ß, TNF-a, and IL-6, plays an important role in osteoarthritis progression. However, the therapeutic failures of recent clinical trials evaluating anti-IL-1, anti-TNF, and anti-IL-6 drugs highlight the lack of overall understanding of the effects of these cytokines on chondrocytes. Here, we generated a comprehensive transcriptomic and proteomic dataset of osteoarthritic chondrocytes treated with these cytokines to describe their pro-inflammatory signature and compare it to the transcriptome of non-osteoarthritic chondrocytes. We first identified specific dysregulation of metabolic-related genes in OA chondrocytes. A metabolic shift, toward increased glycolysis at the expense of mitochondrial respiration, was specifically identified and confirmed by Seahorse® assay of osteoarthritic chondrocytes treated with IL-1ß or TNF-a. These data show a strong association between inflammation and metabolism, indicating that understanding metabolic dysregulations should be a focus of future investigations for the design of therapies for osteoarthritis. Overall design: This experiment compare the gene expression of untreated primary human chondrocytes (control) and treated during 24h with IL-1beta (1ng/mL) or TNF-alpha (25 ng/mL) or IL-6 (50 ng/mL). We used two types of chondrocytes : primary human chondrocytes from OA patients undergoing total knee surgery (OAC) or primary human chondrocytes from non-osteoarthritic joint of patients undergoing scoliotic surgery (NC).