{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:16:38Z","timestamp":1787318198185,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Science and Technology in Regenerative Medicine","award":["302957\/2021-9"],"award-info":[{"award-number":["302957\/2021-9"]}]},{"name":"National Institute of Science and Technology in Regenerative Medicine","award":["305990\/2020-9"],"award-info":[{"award-number":["305990\/2020-9"]}]},{"name":"National Institute of Science and Technology in Regenerative Medicine","award":["2022\/07357-0"],"award-info":[{"award-number":["2022\/07357-0"]}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["302957\/2021-9"],"award-info":[{"award-number":["302957\/2021-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["305990\/2020-9"],"award-info":[{"award-number":["305990\/2020-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2022\/07357-0"],"award-info":[{"award-number":["2022\/07357-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FAPESP","award":["302957\/2021-9"],"award-info":[{"award-number":["302957\/2021-9"]}]},{"name":"FAPESP","award":["305990\/2020-9"],"award-info":[{"award-number":["305990\/2020-9"]}]},{"name":"FAPESP","award":["2022\/07357-0"],"award-info":[{"award-number":["2022\/07357-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells14070489","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T06:25:15Z","timestamp":1742883915000},"page":"489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["TNF-Alpha Inhibitor Prevents Cigarette Smoke Extract-Induced Cell Death in Osteoarthritis-Derived Chondrocytes in Culture"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7492-997X","authenticated-orcid":false,"given":"D\u00e9bora","family":"Levy","sequence":"first","affiliation":[{"name":"Lipids, Oxidation, and Cell Biology Group, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9278-2743","authenticated-orcid":false,"given":"Alexandra Fernandes","family":"Calllera","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Therapeutics, LIM-20, Department of Clinical Medicine, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"},{"name":"Thoracic Surgery Research Laboratory (LIM61), Division of Thoracic Surgery, Heart Institute (InCor), Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyne Riani","family":"Moreira","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Therapeutics, LIM-20, Department of Clinical Medicine, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"},{"name":"Thoracic Surgery Research Laboratory (LIM61), Division of Thoracic Surgery, Heart Institute (InCor), Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5662-7895","authenticated-orcid":false,"given":"Iolanda de F\u00e1tima Lopes Calvo","family":"Tib\u00e9rio","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Therapeutics, LIM-20, Department of Clinical Medicine, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Nogueira","family":"Giglio","sequence":"additional","affiliation":[{"name":"Institute of Orthopedics and Traumatology, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Kawamura","family":"Demange","sequence":"additional","affiliation":[{"name":"Institute of Orthopedics and Traumatology, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7582-5942","authenticated-orcid":false,"given":"Sergio Paulo","family":"Bydlowski","sequence":"additional","affiliation":[{"name":"Lipids, Oxidation, and Cell Biology Group, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-010, Brazil"},{"name":"National Institute of Science and Technology in Regenerative Medicine (INCT-Regenera), CNPq, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6402-3055","authenticated-orcid":false,"given":"Fernanda Degobbi Tenorio Quirino Dos Santos","family":"Lopes","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Therapeutics, LIM-20, Department of Clinical Medicine, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"},{"name":"Thoracic Surgery Research Laboratory (LIM61), Division of Thoracic Surgery, Heart Institute (InCor), Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2019). 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