{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:00:53Z","timestamp":1793412053201,"version":"4.5.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,11,7]],"date-time":"2018-11-07T00:00:00Z","timestamp":1541548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,11,7]],"date-time":"2018-11-07T00:00:00Z","timestamp":1541548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K10460"],"award-info":[{"award-number":["15K10460"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Activation of NF-\u03baB signaling promotes osteoarthritis (OA) through the transcriptional induction of Hif-2\u03b1 and catabolic enzymes. This study sought to examine whether inhibiting I\u03baB\u03b1 kinase (IKK) could suppress the development of surgically-induced OA of the knee in a mouse model. We employed BMS-345541 (4(2\u2032-aminoethyl) amino-1, 8-dimethylimidazo (1,2-a) quinoxaline) as a selective inhibitor of the subunits of IKK. OA was created by resecting the medial collateral ligament and the medial meniscus in the knees of mice. The mice were then treated with an intra-articular injection of BMS-345541 (50\u2009nM to 500\u2009\u00b5M) or vehicle three times a week for 8 weeks. We found that the intra-articular administration of 500\u2009nM and 5\u2009\u00b5M BMS-345541 significantly suppressed OA development. In the BMS-345541-treated cartilage, there was a decrease in the phosphorylation of I\u03baB\u03b1 and the expression of Hif-2\u03b1, Mmp13, and Adamts5. In human articular chondrocytes, the IL-1\u03b2-enhanced expression of Hif-2\u03b1 and catabolic factors were decreased by BMS-345541 treatment in dose-dependent manner. We conclude that the intra-articular administration of BMS-345541 at some concentrations may suppress the development of OA by downregulating signaling through the NF-\u03baB\u2013Hif-2\u03b1 axis.<\/jats:p>","DOI":"10.1038\/s41598-018-34830-9","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T11:18:41Z","timestamp":1541071121000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Intra-articular administration of I\u03baB\u03b1 kinase inhibitor suppresses mouse knee osteoarthritis via downregulation of the NF-\u03baB\/HIF-2\u03b1 axis"],"prefix":"10.1038","volume":"8","author":[{"given":"Yasutaka","family":"Murahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiko","family":"Yano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuma","family":"Makii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kousuke","family":"Iba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Yamashita","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"}]}],"member":"297","published-online":{"date-parts":[[2018,11,7]]},"reference":[{"key":"34830_CR1","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1038\/nature03369","volume":"434","author":"SS Glasson","year":"2005","unstructured":"Glasson, S. 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