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Previous studies have shown that over\u2010expression of matrix\u2010degrading proteinases and proinflammatory cytokines is associated with osteoarthritic cartilage degradation. However, it remains unclear which transcription factors regulate the expression of these cartilage\u2010degrading molecules in articular chondrocytes. This study demonstrated that mice lacking Nfat1, a member of the nuclear factor of activated T cells (NFAT) transcription factors, exhibited normal skeletal development but displayed loss of type II collagen (collagen\u20102) and aggrecan with over\u2010expression of specific matrix\u2010degrading proteinases and proinflammatory cytokines in young adult articular cartilage of load\u2010bearing joints. These initial changes are followed by articular chondrocyte proliferation\/clustering, progressive articular surface destruction, periarticular chondro\u2010osteophyte formation and exposure of thickened subchondral bone, all of which resemble human OA. Forced expression of\n                    <jats:italic>Nfat1<\/jats:italic>\n                    delivered with lentiviral vectors in cultured 3 month\u2010old primary\n                    <jats:italic>Nfat1<\/jats:italic>\n                    knockout (\n                    <jats:italic>Nfat1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) articular chondrocytes partially or completely rescued the abnormal catabolic and anabolic activities of\n                    <jats:italic>Nfat1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    articular chondrocytes. These new findings revealed a previously unrecognized critical role of Nfat1 in maintaining the physiological function of differentiated adult articular chondrocytes through regulating the expression of specific matrix\u2010degrading proteinases and proinflammatory cytokines. Nfat1 deficiency causes OA due to an imbalance between the catabolic and anabolic activities of adult articular chondrocytes, leading to articular cartilage degradation and failed repair activities in and around articular cartilage. These results may provide new insights into the aetiology, pathogenesis and potential therapeutic strategies for osteoarthritis. Copyright \u00a9 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2578","type":"journal-article","created":{"date-parts":[[2009,5,21]],"date-time":"2009-05-21T09:22:01Z","timestamp":1242897721000},"page":"163-172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Transcription factor Nfat1 deficiency causes osteoarthritis through dysfunction of adult articular chondrocytes"],"prefix":"10.1002","volume":"219","author":[{"given":"Jinxi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian 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