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In rheumatoid arthritis, CEMIP is referred to as an angiogenic marker and participates in hyaluronic acid degradation. In this study, CEMIP expression is investigated in healthy and osteoarthritis (OA) cartilage from human and mouse. Its role in OA physiopathology is deciphered, specifically in chondrocytes proliferation and dedifferentiation and in the extracellular matrix remodeling. To this end, CEMIP, \u03b1SMA and types I and III collagen expressions were assessed in human OA and non-OA cartilage. CEMIP expression was also investigated in a mouse OA model. CEMIP expression was studied in vitro using a chondrocyte dedifferentiation model. High-throughput RNA sequencing was performed on chondrocytes after CEMIP silencing. Results showed that CEMIP was overexpressed in human and murine OA cartilage and along chondrocytes dedifferentiation. Most of genes deregulated in CEMIP-depleted cells were involved in cartilage turnover (e.g., collagens), mesenchymal transition and fibrosis. CEMIP regulated \u03b2-catenin protein level. Moreover, CEMIP was essential for chondrocytes proliferation and promoted \u03b1SMA expression, a fibrosis marker, and TGF\u03b2 signaling towards the p-Smad2\/3 (Alk5\/PAI-1) pathway. Interestingly, CEMIP was induced by the pSmad1\/5 (Alk1) pathway. \u03b1SMA and type III collagen expressions were overexpressed in human OA cartilage and along chondrocytes dedifferentiation. Finally, CEMIP was co-expressed in situ with \u03b1SMA in all OA cartilage layers. In conclusion, CEMIP was sharply overexpressed in human and mouse OA cartilage and along chondrocytes dedifferentiation. CEMIP-regulated transdifferentiation of chondrocytes into \u201cchondro-myo-fibroblasts\u201d expressing \u03b1-SMA and type III collagen, two fibrosis markers. Moreover, these \u201cchondro-myo-fibroblasts\u201d were found in OA cartilage but not in healthy cartilage.<\/jats:p>","DOI":"10.1038\/s41419-019-1377-8","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T05:03:53Z","timestamp":1549256633000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes"],"prefix":"10.1038","volume":"10","author":[{"given":"C\u00e9line","family":"Deroyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Charlier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Neuville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Malaise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Kurth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Chariot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Malaise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"de Seny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,4]]},"reference":[{"key":"1377_CR1","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1007\/s10038-003-0079-2","volume":"48","author":"S Abe","year":"2003","unstructured":"Abe, S., Usami, S. & Nakamura, Y. 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