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.

Chronic Obstructive Pulmonary Disease (COPD) is characterized by an abnormal inflammatory response in the airways and alveoli due to prolonged exposure to harmful particles or gases. Despite treatments like bronchodilators and corticosteroids, challenges remain due to the disease’s heterogeneity and medication side effects, such as pulmonary infections. Recent studies suggest that blocking IL-17 could reduce inflammation in lung injury models. This study evaluated the effects of an IL-17 neutralizing antibody in a cigarette smoke-induced COPD mouse model. Mice were exposed to cigarette smoke for 6 months, and treatment with the antibody was initiated in the 5th month. Three experimental groups were formed: control, COPD, and COPD + anti-IL-17. Results showed an increase in the mean linear intercept (Lm) in the COPD group, while treatment with the neutralizing antibody reversed the structural changes. Additionally, the expression of inflammatory cytokines and the RORγt gene was higher in the COPD group. The study concludes that IL-17 neutralizing antibody treatment can reverse functional and structural lung alterations in COPD.

COPD involves progressive airflow limitation driven by chronic inflammation, largely triggered by cigarette smoke. Disease progression is linked to heightened Th17/IL-17 responses, with STAT3 playing a key regulatory role. Targeting STAT3 such as with the selective inhibitor Cryptotanshinone may offer a promising strategy to reduce COPD associated inflammation. This study aimed to evaluate the effects of Cryptotanshinone administration on the Th17 immune response in a murine model of chronic cigarette smoke exposure. C57BL/6 mice were exposed to cigarette smoke for six months, while controls breathed filtered air. From the fourth month, mice received intramuscular Cryptotanshinone treatment. Lung function, airspace enlargement, and STAT3/Th17 responses were assessed through respiratory mechanics, histology, immunohistochemistry, and ELISA. Cigarette-smoke reduced tissue elastance and increased alveolar enlargement. Cryptotanshinone attenuated structural damage but did not improve lung function. Smoke exposure elevated STAT3 and IL-17 positive cells and IL-17 levels, all of which were significantly reduced by treatment, indicating suppression of the STAT3/IL-17 inflammatory axis. Pharmacological inhibition of STAT3 with Cryptotanshinone mitigated structural lung damage and reduced Th17-driven inflammation in a chronic cigarette smoke exposure model. These findings reinforce the importance of the STAT3/Th17 axis in COPD pathogenesis and progression.