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Rheumatoid arthritis (RA) is characterized by chronic synovitis and pannus formation associated with activation of fibroblast-like synoviocytes (FLS). We investigated whether Shh signaling plays a role in the proliferation of FLS in RA. Expression of Shh signaling related components (Shh, Ptch1, Smo, and Gli1) in RA synovial tissues was examined by immunohistochemistry (IHC) and in FLS by IHC, immunofluorescence (IF), quantitative RT-PCR, and western blotting. Expression of Shh, Smo, and Gli1 in RA synovial tissue was higher than that in control tissue (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.05<\/mml:mn><\/mml:math>). Cyclopamine (a specific inhibitor of Shh signaling) decreased mRNA expression of Shh, Ptch1, Smo, and Gli1 in cultured RA FLS, Shh, and Smo protein expression, and significantly decreased FLS proliferation. Flow cytometry analysis suggested that cyclopamine treatment resulted in cell cycle arrest of FLS in G<jats:sub>1<\/jats:sub>phase. Our data show that Shh signaling is activated in synovium of RA patients<jats:italic>in vivo<\/jats:italic>and in cultured FLS form RA patients<jats:italic>in vitro<\/jats:italic>, suggesting a role in the proliferation of FLS in RA. It may therefore be a novel therapeutic target in RA.<\/jats:p>","DOI":"10.1155\/2014\/401903","type":"journal-article","created":{"date-parts":[[2014,3,9]],"date-time":"2014-03-09T05:20:38Z","timestamp":1394342438000},"page":"1-10","source":"Crossref","is-referenced-by-count":30,"title":["Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target"],"prefix":"10.1155","volume":"2014","author":[{"given":"Mingxia","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China"},{"name":"Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China"},{"name":"Department of Rheumatology of Zhongshan Affiliated Hospital, Sun Yat-Sen University, Zhongshan, Guangdong 528400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangling","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixiang","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minqi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuofeng","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, 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