{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:27:11Z","timestamp":1790328431692,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T00:00:00Z","timestamp":1343347200000},"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":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The incidence of low back pain is extremely high and is often linked to intervertebral disc (IVD) degeneration. The mechanism of this disease is currently unknown. This study was undertaken to investigate the role of \u03b2\u2010catenin signaling in IVD tissue function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>\u03b2\u2010catenin protein levels were measured by immunohistochemical analysis of disc samples obtained from patients with disc degeneration and from normal subjects. To generate <jats:italic>\u03b2\u2010catenin<\/jats:italic> conditional activation (cAct) mice, <jats:italic>Col2a1\u2010CreER<\/jats:italic><jats:sup><jats:italic>T2<\/jats:italic><\/jats:sup>\u2013transgenic mice were bred with <jats:italic>\u03b2\u2010catenin<\/jats:italic><jats:sup><jats:italic>fx(Ex3)\/fx(Ex3)<\/jats:italic><\/jats:sup> mice. Changes in disc tissue morphology and function were examined by micro\u2013computed tomography, histologic analysis, and real\u2010time polymerase chain reaction assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>\u03b2\u2010catenin protein was up\u2010regulated in disc tissue samples from patients with disc degeneration. To assess the effects of increased \u03b2\u2010catenin levels on disc tissue, we generated <jats:italic>\u03b2\u2010catenin<\/jats:italic> cAct mice. Overexpression of \u03b2\u2010catenin in disc cells led to extensive osteophyte formation in 3\u2010 and 6\u2010month\u2010old <jats:italic>\u03b2\u2010catenin<\/jats:italic> cAct mice, which were associated with significant changes in the cells and extracellular matrix of disc tissue and growth plate. Gene expression analysis demonstrated that activation of \u03b2\u2010catenin enhanced runt\u2010related transcription factor 2\u2013dependent <jats:italic>Mmp13<\/jats:italic> and <jats:italic>Adamts5<\/jats:italic> expression. Moreover, genetic ablation of <jats:italic>Mmp13<\/jats:italic> or <jats:italic>Adamts5<\/jats:italic> on the <jats:italic>\u03b2\u2010catenin<\/jats:italic> cAct background, or treatment of <jats:italic>\u03b2\u2010catenin<\/jats:italic> cAct mice with a specific matrix metalloproteinase 13 inhibitor, ameliorated the mutant phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that the \u03b2\u2010catenin signaling pathway plays a critical role in disc tissue function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34469","type":"journal-article","created":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T16:05:08Z","timestamp":1331827508000},"page":"2611-2623","source":"Crossref","is-referenced-by-count":96,"title":["Conditional activation of \u03b2\u2010catenin signaling in mice leads to severe defects in intervertebral disc 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