{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:08:30Z","timestamp":1788433710842,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2007,10,29]],"date-time":"2007-10-29T00:00:00Z","timestamp":1193616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To define the roles of transforming growth factor \u03b1 (TGF\u03b1) in cartilage degradation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary rat articular chondrocytes and articular osteochondral explants were cultured with TGF\u03b1 to assess the effects of TGF\u03b1 on chondrocyte physiology and phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TGF\u03b1 altered chondrocyte morphology through reorganization of the actin cytoskeleton and formation of stress fibers. Expression of anabolic genes, including aggrecan, type II collagen, and cartilage link protein, was reduced in response to TGF\u03b1. Proliferation of chondrocytes and formation of articular chondrocyte clusters was stimulated by TGF\u03b1. Expression of matrix metalloproteinase 13 and cathepsin C was increased by TGF\u03b1. We demonstrated the down\u2010regulation of <jats:italic>Sox9<\/jats:italic> messenger RNA and protein levels by TGF\u03b1. This was associated with reduced levels of phosphorylated and total SOX9 in cartilage explants upon TGF\u03b1 treatment. In contrast, another growth factor identified in our microarrays, <jats:italic>Kitl<\/jats:italic>, had no effects on the chondrocyte parameters tested. To examine correlations between the increased levels of TGF\u03b1 in experimental knee osteoarthritis (OA) with the levels of TGF\u03b1 in humans with knee OA, a microarray analysis of mRNA from 13 normal and 12 late\u2010stage OA cartilage samples was performed. Seven OA samples showed <jats:italic>TGFA<\/jats:italic> mRNA levels similar to those in the normal controls, but expression was markedly increased in the other 5 OA samples. These data confirm that <jats:italic>TGFA<\/jats:italic> transcript levels are increased in a subset of patients with OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study adds TGF\u03b1 to the list of dysregulated cytokines present in degrading cartilage in OA. Since TGF\u03b1 inhibits articular chondrocyte anabolic capacity, increases catabolic factors, and contributes to the development of chondrocyte clusters, TGF\u03b1 may be a potential target for therapeutic strategies in the treatment of OA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22968","type":"journal-article","created":{"date-parts":[[2007,10,29]],"date-time":"2007-10-29T15:47:26Z","timestamp":1193672846000},"page":"3693-3705","source":"Crossref","is-referenced-by-count":72,"title":["Transforming growth factor \u03b1 suppression of articular chondrocyte phenotype and <i>Sox9<\/i> expression in a rat model of osteoarthritis"],"prefix":"10.1002","volume":"56","author":[{"given":"C. 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