TNF-Alpha Inhibitor Prevents Cigarette Smoke Extract-Induced Cell Death in Osteoarthritis-Derived Chondrocytes in Culture

Smoking has been associated, among other factors, with musculoskeletal disorders. Although there is no consensus about the effects of smoking on osteoarthritis (OA), the increase in TNF-alpha in smokers has been considered an important factor in OA induction or progression. However, studies on the effects of smoking on chondrocytes are lacking. Here we aimed to study the effects of cigarette smoke extract (CSE) associated with a TNF-alpha inhibitor on cell death of primary human chondrocytes derived from osteoarthritic patients. CSE at 10% led to cell death by apoptosis after 48 h of incubation, together with caspase 3/7 activation, decrease in mitochondrial transmembrane potential, ROS production, and improvement in syndercan-1, perlecan, and RUNX2 gene expression. All these effects promoted by CSE were reversed by TNF-alpha inhibitor. Collagen II, F-actin, and SOX9 were also analyzed, and CSE promoted alteration in the expression of these proteins. In conclusion, our results support the clinical impact of smoking on OA development by showing the detrimental action of CSE on osteoarthritis-derived chondrocytes and the protective effects of TNF-alpha inhibitors, reinforcing the importance of this cytokine in the cartilage injury process.