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However, molecular bases of H<jats:sub>2<\/jats:sub> have not been fully elucidated. Cumulative evidence indicates that H<jats:sub>2<\/jats:sub> acts as a gaseous signal modulator. We found that H<jats:sub>2<\/jats:sub> suppresses activated Wnt\/\u03b2-catenin signaling by promoting phosphorylation and degradation \u03bff \u03b2-catenin. Either complete inhibition of GSK3 or mutations at CK1- and GSK3-phosphorylation sites of \u03b2-catenin abolished the suppressive effect of H<jats:sub>2<\/jats:sub>. H<jats:sub>2<\/jats:sub> did not increase GSK3-mediated phosphorylation of glycogen synthase, indicating that H<jats:sub>2<\/jats:sub> has no direct effect on GSK3 itself. Knock-down of adenomatous polyposis coli (APC) or Axin1, which form the \u03b2-catenin degradation complex, minimized the suppressive effect of H<jats:sub>2<\/jats:sub> on \u03b2-catenin accumulation. Accordingly, the effect of H<jats:sub>2<\/jats:sub> requires CK1\/GSK3-phosphorylation sites of \u03b2-catenin, as well as the \u03b2-catenin degradation complex comprised of CK1, GSK3, APC and Axin1. We additionally found that H<jats:sub>2<\/jats:sub> reduces the activation of Wnt\/\u03b2-catenin signaling in human osteoarthritis chondrocytes. Oral intake of H<jats:sub>2<\/jats:sub> water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating \u03b2-catenin accumulation. We first demonstrate that H<jats:sub>2<\/jats:sub> suppresses abnormally activated Wnt\/\u03b2-catenin signaling, which accounts for the protective roles of H<jats:sub>2<\/jats:sub> in a fraction of diseases.<\/jats:p>","DOI":"10.1038\/srep31986","type":"journal-article","created":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T09:19:43Z","timestamp":1472116783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Molecular hydrogen suppresses activated Wnt\/\u03b2-catenin signaling"],"prefix":"10.1038","volume":"6","author":[{"given":"Yingni","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bisei","family":"Ohkawara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikako","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuaki","family":"Misawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Takegami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Masuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Toyokuni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinji","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,25]]},"reference":[{"key":"BFsrep31986_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13618-015-0035-1","volume":"5","author":"M Ichihara","year":"2015","unstructured":"Ichihara, M. et al. 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