Inhalation of cigarette smoke induces structural changes in the murine knee joint via increased expression of TNF-alpha

Abstract

Smoking is a major risk factor for cardiovascular, pulmonary, and musculoskeletal diseases, accelerating tissue degradation. It increases TNF-alpha expression, a cytokine with catabolic effects on cartilage, contributing to joint degeneration. This study evaluates smoking-induced TNF-alpha upregulation in osteochondral tissues, investigating the associated cellular and molecular mechanisms. Thirty-two male C57BL/6 mice (6–8 weeks old) were divided into four groups: Control, exposed to filtered air; Smoking, exposed to cigarette smoke (30 min/day, 5 days/ week, for 45 consecutive days); Control + TNF-alpha inhibitor, exposed to filtered air and treated weekly with Adalimumab; and Smoking + TNFalpha inhibitor, exposed to cigarette smoke and treated with Adalimumab. Femorotibial joints were subjected to histomorphometry, histology, ELISA (TNF-alpha, OPG, RANKL), and immunofluorescence (type I and II collagen). Smoking did not reduce cartilage area but led to decreased chondrocyte density, subchondral bone area, and collagen types I and II. TNF-alpha and RANKL levels increased in the Smoking group but were reversed/protected by Adalimumab, which restored cartilage and bone parameters, preventing further damage. These findings reinforce TNFalpha as a therapeutic target in osteochondral diseases and highlight the relevance of anti-TNF therapies.