{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:28:18Z","timestamp":1790422098018,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG044034"],"award-info":[{"award-number":["AG044034"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR049003"],"award-info":[{"award-number":["AR049003"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"Objective<\/jats:title>To determine the role of JNK<\/jats:styled-content> signaling in the development of osteoarthritis (OA<\/jats:styled-content>) induced by joint injury or aging in mice.<\/jats:p><\/jats:sec>Methods<\/jats:title>In the joint injury model, 12\u2010week\u2010old wild\u2010type control, JNK<\/jats:styled-content>1\u2212\/\u2212<\/jats:sup>, JNK<\/jats:styled-content>2\u2212\/\u2212<\/jats:sup>, and JNK<\/jats:styled-content>1fl\/fl<\/jats:sup>JNK<\/jats:styled-content>2\u2212\/\u2212<\/jats:sup> aggecan\u2010CreERT<\/jats:sup><\/jats:styled-content>2<\/jats:sup> double\u2010knockout mice were subjected to destabilization of the medial meniscus (DMM<\/jats:styled-content>) (n = 15 mice per group) or sham surgery (n = 9\u201310 mice per group), and OA<\/jats:styled-content> was evaluated 8 weeks later. In the aging experiment, wild\u2010type control, JNK<\/jats:styled-content>1\u2212\/\u2212<\/jats:sup>, and JNK<\/jats:styled-content>2\u2212\/\u2212<\/jats:sup> mice (n = 15 per group) were evaluated at 18 months of age. Mouse knee joints were evaluated by scoring articular cartilage structure, toluidine blue staining, osteophytes, and synovial hyperplasia, by histomorphometric analysis, and by immunostaining for the senescence marker p16INK<\/jats:sup><\/jats:styled-content>4a<\/jats:sup>. Production of matrix metalloproteinase 13 (MMP<\/jats:styled-content>\u201013) in cartilage explants in response to fibronectin fragments was measured by enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec>Results<\/jats:title>There were no differences after DMM<\/jats:styled-content> surgery between the wild\u2010type and the JNK<\/jats:styled-content>\u2010knockout mouse groups in articular cartilage structure, toluidine blue, or osteophyte scores or in MMP<\/jats:styled-content>\u201013 production in explants. All 3 knockout mouse groups had increased subchondral bone thickness and area of cartilage necrosis compared to wild\u2010type mice. Aged JNK<\/jats:styled-content>\u2010knockout mice had significantly worse articular cartilage structure scores compared to the aged wild\u2010type control mice (mean \u00b1 SD<\/jats:styled-content> 52 \u00b1 24 in JNK<\/jats:styled-content>1\u2212\/\u2212<\/jats:sup> mice and 60 \u00b1 25 in JNK<\/jats:styled-content>2\u2212\/\u2212<\/jats:sup> mice versus 32 \u00b1 18 in controls; P<\/jats:italic> = 0.02 and P<\/jats:italic> = 0.004, respectively). JNK<\/jats:styled-content>1\u2212\/\u2212<\/jats:sup> mice also had higher osteophyte scores. Deletion of JNK<\/jats:styled-content><\/jats:italic> resulted in increased expression of p16INK<\/jats:sup><\/jats:styled-content>4a<\/jats:sup> in the synovium and cartilage in older mice.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>JNK<\/jats:styled-content>1 and JNK<\/jats:styled-content>2 are not required for the development of OA<\/jats:styled-content> in the mouse DMM<\/jats:styled-content> model. Deletion of JNK<\/jats:styled-content>1<\/jats:italic> or JNK<\/jats:styled-content>2<\/jats:italic> is associated with more severe age\u2010related OA<\/jats:styled-content> and increased cell senescence, suggesting that JNK<\/jats:styled-content> may act as a negative regulator of senescence in the joint.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41312","type":"journal-article","created":{"date-parts":[[2020,5,17]],"date-time":"2020-05-17T10:10:57Z","timestamp":1589710257000},"page":"1679-1688","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Deletion of JNK Enhances Senescence in Joint Tissues and Increases the Severity of Age\u2010Related Osteoarthritis in Mice"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2832-6144","authenticated-orcid":false,"given":"Richard F.","family":"Loeser","sequence":"first","affiliation":[{"name":"University of North Carolina School of 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