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Fibrosis of the synovial tissue is often detected and considered one of the main causes of joint stiffness and pain. In our earlier proteomic study, increased levels of vitronectin (VTN) fragment (amino acids 381\u2013397) were observed in the serum of osteoarthritis patients. In this work, the affinity of this fragment for integrins and its putative role in TGF-\u03b21 activation were investigated. A competition study determined the interaction of VTN<jats:sub>(381\u2013397 a.a.)<\/jats:sub> with \u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>6<\/jats:sub> integrin. Subsequently, the presence of \u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>6<\/jats:sub> integrin was substantiated on primary human fibroblast-like synoviocytes (FLSs) by western blot and flow cytometry. By immunohistochemistry, \u03b2<jats:sub>6<\/jats:sub> was detected in synovial membranes, and its expression showed a correlation with tissue fibrosis. Moreover, \u03b2<jats:sub>6<\/jats:sub> expression was increased under TGF-\u03b21 stimulation; hence, a TGF-\u03b2 bioassay was applied. We observed that \u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>6<\/jats:sub> could mediate TGF-\u03b21 bioavailability and that VTN<jats:sub>(381\u2013397 a.a.)<\/jats:sub> could prevent TGF-\u03b21 activation by interacting with \u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>6<\/jats:sub> in human FLSs and increased \u03b1-SMA. Finally, we analyzed serum samples from healthy controls and patients with osteoarthritis and other rheumatic diseases by nano-LC\/Chip MS\u2013MS, confirming the increased expression of VTN<jats:sub>(381\u2013397 a.a.)<\/jats:sub> in osteoarthritis as well as in lupus erythematosus and systemic sclerosis. These findings corroborate our previous observations concerning the overexpression of VTN<jats:sub>(381\u2013397 a.a.)<\/jats:sub> in osteoarthritis but also in other rheumatic diseases. This fragment interacts with \u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>6<\/jats:sub> integrin, a receptor whose expression is increased in FLSs from the osteoarthritic synovial membrane and that can mediate the activation of the TGF-\u03b21 precursor in human FLSs.<\/jats:p>","DOI":"10.1038\/s12276-021-00558-2","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T09:06:39Z","timestamp":1612170399000},"page":"210-222","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Modulation of \u03b1V\u03b26 integrin in osteoarthritis-related synovitis and the interaction with VTN(381\u2013397 a.a.) competing for TGF-\u03b21 activation"],"prefix":"10.1038","volume":"53","author":[{"given":"Federica","family":"Ciregia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Deroyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebl","family":"Cobraiville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelda","family":"Plener","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":"Marianne","family":"Fillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel G.","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":[[2021,2,1]]},"reference":[{"key":"558_CR1","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","volume":"393","author":"DJ Hunter","year":"2019","unstructured":"Hunter, D. 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