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Despite a successful clinical trial with an oral Smad7 antisense oligonucleotide in CD, intraarticular (i.a.) modulation of Smad7 expression has not been performed in rheumatoid joint yet. In this study, contradictory to the findings in CD mucosa, higher levels of pSmad2\/3 were found in RA synovium. <jats:italic>In vitro<\/jats:italic> experiments with synovial fibroblasts revealed that higher acetylated Smad7 expression was associated with lower activation status. Abundant expression of synovial pSmad2\/3 with increased levels during the progression of arthritis was detected in collagen-induced arthritis (CIA) mice. To prove the concept that overexpressing Smad7 as a therapeutic strategy in rheumatoid joint, the i.a. injection of lentiviral vectors carrying Smad7 (LVSmad7) was carried out in CIA mice. In LVSmad7-injected joints, there were lower arthritis and histological scores with less synovitis, synovial hyperplasia and erosion on cartilage and bone as well as reduced IL-17 and TNF expression levels in comparison with other control groups. In conclusion, we demonstrate that lentiviral vector-mediated i.a. overexpression of Smad7 can ameliorate rheumatoid joint, implicating a pharmacological development of Smad7-based molecular strategy in RA.<\/jats:p>","DOI":"10.1038\/srep35163","type":"journal-article","created":{"date-parts":[[2016,10,12]],"date-time":"2016-10-12T09:42:27Z","timestamp":1476265347000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Intraarticular overexpression of Smad7 ameliorates experimental arthritis"],"prefix":"10.1038","volume":"6","author":[{"given":"Shih-Yao","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-Li","family":"Shiau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Liang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrong-Reen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,12]]},"reference":[{"key":"BFsrep35163_CR1","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1042\/CS20110086","volume":"121","author":"JF Santiba\u00f1ez","year":"2011","unstructured":"Santiba\u00f1ez, J. 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