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Previously, we reported that Runx1 enhanced chondrogenic differentiation through transcriptional induction of<jats:italic>COL2A1<\/jats:italic>, and suppressed hypertrophic differentiation. Here, we investigated the involvement of Runx1 in OA development as well as its potential underlying molecular mechanism. When we analysed OA development in<jats:italic>Col2a1-Cre;Runx1<\/jats:italic><jats:sup><jats:italic>fl\/fl<\/jats:italic><\/jats:sup>and<jats:italic>Runx1<\/jats:italic><jats:sup><jats:italic>fl\/fl<\/jats:italic><\/jats:sup>mice by surgically inducing joint instability, Cartilage degradation and osteophyte formation of<jats:italic>Col2a1-Cre;Runx1<\/jats:italic><jats:sup><jats:italic>fl\/fl<\/jats:italic><\/jats:sup>joints was accelerated compared with joints in<jats:italic>Runx1<\/jats:italic><jats:sup><jats:italic>fl\/fl<\/jats:italic><\/jats:sup>animals 8 weeks after surgery. To investigate chondrocyte regulation by Runx1, we analysed interactions with co-factors and downstream molecules. Runx1 enhanced cartilage matrix production in cooperation with Sox5, Sox6, and Sox9, and co-immunoprecipitation assays showed protein\u2013protein binding between Runx1 and each Sox protein. Knockdown of Runx1 increased expression of a hypertrophic marker, Co10a1, in mouse articular cartilage and primary chondrocytes. This expression was accompanied by decreased expression of Bapx1, a potent suppressor of hypertrophic differentiation. Notably, Runx1-induced suppression of hypertrophic differentiation was diminished by siRNA silencing of<jats:italic>Bapx1<\/jats:italic>, whereas chondrogenic markers were unaltered. Thus, Runx1 contributes to articular cartilage maintenance by enhancing matrix production in cooperation with Sox proteins, and suppressing hypertrophic differentiation at least partly via Bapx1 induction.<\/jats:p>","DOI":"10.1038\/s41598-019-43948-3","type":"journal-article","created":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T10:11:42Z","timestamp":1558433502000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Runx1 contributes to articular cartilage maintenance by enhancement of cartilage matrix production and suppression of hypertrophic differentiation"],"prefix":"10.1038","volume":"9","author":[{"given":"Fumiko","family":"Yano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Ohba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Murahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakae","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ung-il","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,5,21]]},"reference":[{"key":"43948_CR1","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nature01657","volume":"423","author":"HM Kronenberg","year":"2003","unstructured":"Kronenberg, H. 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