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

Author(s): Alexandra Fernandes Callera, Alex Ferreira da Silva, Alyne Riani Moreira, Francine Maria de Almeida, Ana Luiza Porfirio, Camila Uchoa da Silva, Cíntia do Nascimento da Silva, Vitor Daniel Rodrigues de Souza, Débora Levy, Alexandre Povoa Barbosa, Ana Paula Pereira Velosa, Walcy RosoliaTeodoro, Iolanda de Fátima Calvo Tibério, Fernanda Deggobi T.Q.S. Lopes

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.