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Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-\u03b21 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (<jats:italic>COL1A1<\/jats:italic>, <jats:italic>TIMP-1<\/jats:italic>, and <jats:italic>ACTA-2<\/jats:italic>) and those related to inflammation (<jats:italic>IL-6<\/jats:italic> and <jats:italic>TNF-\u03b1<\/jats:italic>) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, \u03b1-SMA (coded by <jats:italic>ACTA-2<\/jats:italic>), IL-6 and TNF-\u03b1 were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (<jats:italic>COL1A1<\/jats:italic>, <jats:italic>TIMP-1<\/jats:italic>, and <jats:italic>ADAM-12<\/jats:italic>) and inflammation (<jats:italic>IL-6<\/jats:italic> and <jats:italic>TNF-\u03b1<\/jats:italic>) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&amp;E, Masson\u2019s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The proliferation of FLSs was greatest when induced with 2.5\u00a0ng\/ml TGF-\u03b21 although it did not promote their migration. Therefore, 2.5\u00a0ng\/ml TGF-\u03b21 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0\u00a0mg\/ml. PFD decreased the expression of COL1A1 while TGF-\u03b21 increased both mRNA and protein expression levels of IL-6 but had no effect on \u03b1-SMA or TNF-\u03b1 expression. PFD decreased mRNA expression levels of <jats:italic>COL1A1<\/jats:italic>, <jats:italic>IL-6<\/jats:italic>, and <jats:italic>TNF-\u03b1 <\/jats:italic>in vivo. H&amp;E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson\u2019s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-021-02823-4","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T11:04:53Z","timestamp":1618830293000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Pirfenidone attenuates synovial fibrosis and postpones the progression of osteoarthritis by anti-fibrotic and anti-inflammatory properties in vivo and in vitro"],"prefix":"10.1186","volume":"19","author":[{"given":"Qilu","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanshuai","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunzheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"2823_CR1","doi-asserted-by":"publisher","first-page":"3521","DOI":"10.1002\/jcp.30091","volume":"236","author":"Z Zhou","year":"2021","unstructured":"Zhou Z, Ma J, Lu J, Chen A, Zhu L. 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All animal experiments were approved by the institutional animal care and use committee of Xi\u2019an Jiaotong University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"157"}}