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Notably, sustained rAAV production of TGF-\u03b2 in OA cartilage advantageously reduced the expression of key OA-associated markers of chondrocyte hypertrophic and terminal differentiation (type-X collagen, MMP-13, PTHrP, \u03b2-catenin) while increasing that of protective TIMPs and of the TGF-\u03b2 receptor I in a manner that restored a favorable ALK1\/ALK5 balance. Of note, the levels of activities in TGF-\u03b2-treated OA cartilage were higher than those of normal cartilage, suggesting that further optimization of the candidate treatment (dose, duration, localization, presence of modulating co-factors) will most likely be necessary to reproduce an original cartilage surface in relevant models of experimental OA<jats:italic>in vivo<\/jats:italic>without triggering potentially adverse effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present findings show the ability of rAAV-mediated TGF-\u03b2 gene transfer to directly remodel human OA cartilage by activating the biological, reparative activities and by regulating hypertrophy and terminal differentiation in damaged chondrocytes as a potential treatment for OA or for other disorders of the cartilage that may require transplantation of engineered cells.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1479-5876-11-211","type":"journal-article","created":{"date-parts":[[2013,9,13]],"date-time":"2013-09-13T16:14:42Z","timestamp":1379088882000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["rAAV-mediated overexpression of TGF-\u03b2 stably restructures human osteoarthritic articular cartilage in situ"],"prefix":"10.1186","volume":"11","author":[{"given":"Jagadeesh K","family":"Venkatesan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Rey-Rico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertrud","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wezel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Madry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Cucchiarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,9,13]]},"reference":[{"key":"1607_CR1","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1002\/art.34453","volume":"64","author":"RF Loeser","year":"2012","unstructured":"Loeser RF, Goldring SR, Scanzello CR, Goldring MB: Osteoarthritis: a disease of the joint as an organ. 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