{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:14:01Z","timestamp":1790172841014,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T00:00:00Z","timestamp":1450828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"DFG (Emmy Noether Programme grant)"},{"name":"European Union (Seventh Framework Programme projects Adipoa, Masterswitch, and Marie Curie ITN Osteoimmune, and the Innovative Medicines Initiative project BTCure)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether overexpression of the activator protein 1 (AP\u20101) transcription factor Fra\u20101 in adipose\u2010derived stromal cells (ADSCs) is an effective treatment of collagenase\u2010induced osteoarthritis (OA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>OA was induced by injection of collagenase into the knee joints of male C57BL\/6 mice. ADSCs were isolated from the inguinal fat pads of 8\u2010week\u2010old wild\u2010type or Fra\u20101\u2013transgenic mice and injected into the knee joints of mice with collagenase\u2010induced OA 7 days after OA induction. Histologic analyses of cartilage destruction and chondrocyte cell death were performed. Adipogenic differentiation capacity was evaluated, gene expression was analyzed, and cytokine profiling was performed in stromal vascular fractions (SVFs) and ADSCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>OA\u2010related cartilage destruction and chondrocyte cell death were significantly reduced in mouse knee joints treated with ADSCs from Fra\u20101\u2013transgenic mice compared to mouse knee joints treated with ADSCs from wild\u2010type mice. This effect did not result from the higher number of adipogenic progenitors observed in SVFs from Fra\u20101\u2013transgenic compared to wild\u2010type mouse fat pads, since injection of wild\u2010type mouse ADSCs enriched for adipogenic progenitors did not show any additional chondroprotective effects compared to nonsorted ADSCs. However, Fra\u20101\u2013transgenic mouse ADSCs showed decreased adipogenic differentiation capacity. Moreover, Fra\u20101 significantly inhibited proinflammatory interleukin\u20106 and pentraxin 3 expression, while increasing the expression of extracellular matrix proteins, such as periostin and spondin 1. These findings suggest that Fra\u20101 overexpression leads to an increased chondroprotective effect of ADSCs in OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ADSCs overexpressing Fra\u20101 effectively protect against OA. Our data indicate that genetic modifications of ADSCs, such as Fra\u20101 overexpression, may improve their potential to protect articular cartilage against OA\u2010mediated damage.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39425","type":"journal-article","created":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T12:54:55Z","timestamp":1441976095000},"page":"138-151","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of Osteoarthritis by Adipose\u2010Derived Stromal Cells Overexpressing Fra\u20101 in Mice"],"prefix":"10.1002","volume":"68","author":[{"given":"Kay","family":"Schwabe","sequence":"first","affiliation":[{"name":"University of Erlangen\u2013Nuremberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Garcia","sequence":"additional","affiliation":[{"name":"University of Erlangen\u2013Nuremberg Erlangen 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