{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:50:31Z","timestamp":1770835831632,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,15]],"date-time":"2018-11-15T00:00:00Z","timestamp":1542240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600840"],"award-info":[{"award-number":["81600840"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771047"],"award-info":[{"award-number":["81771047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Connexin\u2010mediated functional gap junction intercellular communication (GJIC) has a vital role in development, homeostasis and pathology. Transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21), as one of the most vital factors in chondrocytes, promotes cartilage precursor cell differentiation and chondrocyte proliferation, migration and metabolism. However, how TGF\u2010\u03b21 mediates GJIC in chondrocytes remains unclear. This study aims to determine the influence of TGF\u2010\u03b21 on GJIC in mouse chondrocytes and its underlying mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>qPCR and mRNA microarray were used to verify the expression of genes in the TGF\u2010\u03b2 and connexin families in cartilage and chondrocytes. A scrape loading\/dye transfer assay was performed to explore GJIC. Western blot analysis was used to detect connexin43 (Cx43) and Smad signalling components. Immunofluorescence staining was performed to characterize protein distribution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The TGF\u2010\u03b21 mRNA was the highest expressed member of the TGF\u03b2 super family in cartilage. TGF\u2010\u03b21 promoted functional GJIC through increased expression of Cx43. TGF\u2010\u03b21\u2010mediated GJIC required the participation of TGF\u2010\u03b2 type I receptor. TGF\u2010\u03b21 activated Smad3 and Smad4 signalling to facilitate their nuclear translocation. The Smad3 and Smad4 signalling proteins bound to the promoter of <jats:italic>Gja1<\/jats:italic> and thus initiated Cx43 gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>For the first time, these results revealed a vital role of TGF\u2010\u03b21 in cell\u2010cell communication in chondrocytes via gap junction formation. We describe the regulatory mechanism, the involvement of TGF\u2010\u03b2 type I receptor and the nuclear translocation of Smad3\/4.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.12544","type":"journal-article","created":{"date-parts":[[2018,11,16]],"date-time":"2018-11-16T02:21:16Z","timestamp":1542334876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["TGF\u2010\u03b21 promotes gap junctions formation in chondrocytes via Smad3\/Smad4 signalling"],"prefix":"10.1111","volume":"52","author":[{"given":"Qingxuan","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Orthodontics Department, West China Hospital of Stomatology Sichuan University Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenchen","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Orthodontics Department, West China 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