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However, the role of RXR\u03b1 in the pathophysiology of OA remains unknown. The present study aimed to investigate whether RXR\u03b1 modulator, such as K-80003 can treat OA. Experimental OA was induced by intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats. Articular cartilage degeneration was assessed using Safranin-O and fast green staining. Synovial inflammation was measured using hematoxylin and eosin (H&amp;E) staining and enzyme-linked immunosorbent assay (ELISA). Expressions of MMP-13, ADAMTS-4 and ER\u03b1 in joints were analyzed by immunofluorescence staining. Western blot, RT-PCR and co-Immunoprecipitation (co-IP) were used to assess the effects of K-80003 on RXR\u03b1-ER\u03b1 interaction. Retinoid X receptor \u03b1 (RXR\u03b1) modulator K\u201080003 prevented the degeneration of articular cartilage, reduced synovial inflammation, and alleviated osteoarthritic pain in rats. Furthermore, K-80003 markedly inhibited IL-1\u03b2\u2010induced p65 nuclear translocation and I\u03baB\u03b1 degradation, and down-regulate the expression of HIF-2\u03b1, proteinases (MMP9, MMP13, ADAMTS-4) and pro-inflammatory factors (IL-6 and TNF\u03b1) in primary chondrocytes. Additionally, knockdown of ER\u03b1 with siRNA blocked these effects of K-80003 in chondrocytes. In conclusion, RXR\u03b1 modulators K-80003 suppresses inflammatory and catabolic responses in OA, suggesting that targeting RXR\u03b1\u2010ER\u03b1 interaction by RXR\u03b1 modulators might be a novel therapeutic approach for OA treatment.<\/jats:p>","DOI":"10.1038\/s41598-021-96517-y","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T10:03:20Z","timestamp":1629453800000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The retinoid X receptor \u03b1 modulator K-80003 suppresses inflammatory and catabolic responses in a rat model of osteoarthritis"],"prefix":"10.1038","volume":"11","author":[{"given":"Hua","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junnan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaofang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"96517_CR1","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/s41584-018-0095-4","volume":"14","author":"M Marshall","year":"2018","unstructured":"Marshall, M., Watt, F. 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