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Cardamonin (CD) is a natural flavonoid isolated from <jats:italic>Alpinia katsumadai<\/jats:italic> that has anti\u2010inflammatory activity. The objectives of this study were to investigate the therapeutic effects and potential mechanism of CD in regulating OA subchondral osteosclerosis at in vivo and in vitro settings. Eight\u2010week\u2010old male C57BL\/6J mice were randomly divided into four groups: sham operation, anterior cruciate ligament transection (ACLT)\u2010induced OA model, low\u2010dose and high\u2010dose CD treated ACLT\u2010OA model groups. Histological assessment and immunohistochemical examinations for chondrocyte metabolism\u2010related markers metalloproteinase\u201013, ADAMTS\u20104, Col II, and Sox\u20109 were performed. Microcomputed tomography was used to assess the sclerosis indicators in subchondral bone. Further, MC3T3\u2010E1 (a mouse calvarial preosteoblast cell line) cells were treated with various concentrations of CD to reveal the influence and potential molecular pathways of CD in osteogenic differentiations. Animal studies suggested that CD alleviated the pathological changes in OA mice such as maintaining integrity and increasing the thickness of hyaline cartilage, decreasing the thickness of calcified cartilage, decreasing the Osteoarthritis Research Society International score, regulating articular cartilage metabolism, and inhibiting subchondral osteosclerosis. In vitro investigation indicated that CD inhibited alkaline phosphatase expression and production of calcium nodules during osteogenic differentiation of MC3T3\u2010E1 cells. In addition, CD inhibited the expression of osteogenic differentiation\u2010related indicators and Wnt\/\u03b2\u2010catenin pathway\u2010related proteins. In conclusion, CD inhibits osteogenic differentiation by downregulating Wnt\/\u03b2\u2010catenin signaling and alleviating subchondral osteosclerosis in a mouse model of OA.<\/jats:p>","DOI":"10.1002\/jor.25842","type":"journal-article","created":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T16:15:13Z","timestamp":1711210513000},"page":"1933-1942","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cardamonin inhibits osteogenic differentiation by downregulating Wnt\/beta\u2010catenin signaling and alleviates subchondral osteosclerosis in osteoarthritic mice"],"prefix":"10.1002","volume":"42","author":[{"given":"Fanding","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Hand and Foot Surgery, Shandong Provincial Hospital Shandong University Jinan Shandong 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