{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:03:37Z","timestamp":1788185017682,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["Ricerca Corrente L4169 and L4165"],"award-info":[{"award-number":["Ricerca Corrente L4169 and L4165"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Connexin 43 (Cx43) is crucial for the development and homeostasis of the musculoskeletal system, where it plays multifaceted roles, including intercellular communication, transcriptional regulation and influencing osteogenesis and chondrogenesis. Here, we investigated Cx43 modulation mediated by inflammatory stimuli involved in osteoarthritis, i.e., 10 ng\/mL Tumor Necrosis Factor alpha (TNF\u03b1) and\/or 1 ng\/mL Interleukin-1 beta (IL-1\u03b2), in primary chondrocytes (CH) and osteoblasts (OB). Additionally, we explored the impact of synovial fluids from osteoarthritis patients in CH and cartilage explants, providing a more physio-pathological context. The effect of TNF\u03b1 on Cx43 expression in cartilage explants was also assessed. TNF\u03b1 downregulated Cx43 levels both in CH and OB (\u221273% and \u221232%, respectively), while IL-1\u03b2 showed inconclusive effects. The reduction in Cx43 levels was associated with a significant downregulation of the coding gene GJA1 expression in OB only (\u221265%). The engagement of proteasome in TNF\u03b1-induced effects, already known in CH, was also observed in OB. TNF\u03b1 treatment significantly decreased Cx43 expression also in cartilage explants. Of note, Cx43 expression was halved by synovial fluid in both CH and cartilage explants. This study unveils the regulation of Cx43 in diverse musculoskeletal cell types under various stimuli and in different contexts, providing insights into its modulation in inflammatory joint disorders.<\/jats:p>","DOI":"10.3390\/ijms25158547","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T18:21:40Z","timestamp":1722882100000},"page":"8547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Connexin 43 Modulation in Human Chondrocytes, Osteoblasts and Cartilage Explants: Implications for Inflammatory Joint Disorders"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1361-168X","authenticated-orcid":false,"given":"Elena","family":"Della Morte","sequence":"first","affiliation":[{"name":"Laboratory of Biotechnological Applications, IRCCS Istituto Ortopedico Galeazzi, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7186-7432","authenticated-orcid":false,"given":"Chiara","family":"Giannasi","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnological Applications, IRCCS Istituto Ortopedico Galeazzi, 20157 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20129 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Valenza","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnological Applications, IRCCS Istituto Ortopedico Galeazzi, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1658-8932","authenticated-orcid":false,"given":"Francesca","family":"Cadelano","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnological Applications, IRCCS Istituto Ortopedico Galeazzi, 20157 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20129 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Aldegheri","sequence":"additional","affiliation":[{"name":"Hip Department, IRCCS Istituto Ortopedico Galeazzi, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Zagra","sequence":"additional","affiliation":[{"name":"Hip Department, IRCCS Istituto Ortopedico Galeazzi, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3655-9968","authenticated-orcid":false,"given":"Stefania","family":"Niada","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnological Applications, IRCCS Istituto Ortopedico Galeazzi, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7848-8099","authenticated-orcid":false,"given":"Anna Teresa","family":"Brini","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnological Applications, IRCCS Istituto Ortopedico Galeazzi, 20157 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20129 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1016\/j.bbamem.2018.02.023","article-title":"Regulation of phase boundaries and phase-segregated patterns in model membranes","volume":"1860","author":"Fanani","year":"2018","journal-title":"Biochim. 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