{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T21:25:51Z","timestamp":1773869151474,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,8,13]],"date-time":"2023-08-13T00:00:00Z","timestamp":1691884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dysregulation of Wingless and Int\u20101 (Wnt) signaling has been strongly associated with development and progression of osteoarthritis (OA). Here, we set out to investigate the independent effects of either mechanical stress (MS) or inflammation on Wnt signaling in human neocartilage pellets, and to relate this Wnt signaling to OA pathophysiology. OA synovium\u2010conditioned media (OAS\u2010CM) was collected after incubating synovium from human end\u2010stage OA joints for 24\u2009h in medium. Cytokine levels in the OAS\u2010CM were determined with a multiplex immunoassay (Luminex). Human neocartilage pellets were exposed to 20% MS, 2% OAS\u2010CM or 1\u2009ng\/mL Interleukin\u20101\u03b2\u00a0(IL\u20101\u03b2). Effects on expression levels of Wnt signaling members were determined by reverse transcription\u2010quantitative polymerase chain reaction. Additionally, the expression of these members in articular cartilage from human OA joints was analyzed in association with joint space narrowing (JSN) and osteophyte scores. Protein levels of IL\u20101\u03b2, IL\u20106, IL\u20108, IL\u201010, tumor necrosis factor \u03b1, and granulocyte\u2010macrophage colony\u2010stimulating factor positively correlated with each other. MS increased noncanonical <jats:italic>WNT5A<\/jats:italic> and <jats:italic>FOS<\/jats:italic> expression. In contrast, these genes were downregulated upon stimulation with OAS\u2010CM or IL\u20101\u03b2. Furthermore, Wnt inhibitors <jats:italic>DKK1<\/jats:italic> and <jats:italic>FRZB<\/jats:italic> decreased in response to OAS\u2010CM or IL\u20101\u03b2 exposure. Finally, expression of <jats:italic>WNT5A<\/jats:italic> in OA articular cartilage was associated with increased JSN scores, but not osteophyte scores. Our results demonstrate that MS and inflammatory stimuli have opposite effects on canonical and noncanonical Wnt signaling in human neocartilage. Considering the extent to which MS and inflammation contribute to OA in individual patients, we hypothesize that targeting specific Wnt pathways offers a more effective, individualized approach.<\/jats:p>","DOI":"10.1002\/jor.25673","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T05:02:01Z","timestamp":1690866121000},"page":"286-295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mechanical stress and inflammation have opposite effects on Wnt signaling in human chondrocytes"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0787-0856","authenticated-orcid":false,"given":"Ritchie G. 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