{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:21:17Z","timestamp":1791422477432,"version":"4.3.3"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,10,26]],"date-time":"2014-10-26T00:00:00Z","timestamp":1414281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007380","name":"Fondation de l'Avenir","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007380","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Union Seventh Framework Programme (project Sybil)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Wnt signaling is a master regulator of joint homeostasis, but its role in osteoarthritis (OA) remains unclear. This study was undertaken to characterize the activation of Wnt\/\u03b2\u2010catenin in knee joints of mice with OA and to assess how inhibiting this pathway in bone could affect cartilage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>OA was induced by partial meniscectomy in Topgal mice and in transgenic mice overexpressing Dkk\u20101 under the control of the 2.3\u2010kb Col1a1 promoter (Col1a1\u2010Dkk\u20101\u2013Tg mice). Wnt\/\u03b2\u2010catenin activation was assessed by X\u2010Gal staining at baseline and at weeks 4, 6, and 9. Cartilage and bone damage was analyzed in Col1a1\u2010Dkk\u20101\u2013Tg mice with OA at week 6. Primary chondrocytes and cartilage explants were used to assess the effect of Dkk\u20101 on cartilage catabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In meniscectomized Topgal mice, Wnt was mainly activated in osteocytes from the subchondral bone at week 6 after OA induction, as well as in osteophytes and synovium at week 4. Chondrocytes from damaged zones expressed X\u2010Gal from week 4. Dkk\u20101 expression was high in chondrocytes in control mouse knees (mean \u00b1 SEM 84.2 \u00b1 3.1%) but decreased greatly in knees of meniscectomized mice from week 4 (mean \u00b1 SEM 14.4 \u00b1 3.8%). The OA score was lower in meniscectomized Col1a1\u2010Dkk\u20101\u2013Tg mice at week 6 compared with wild\u2010type mice (5.1 \u00b1 0.6 versus 8.4 \u00b1 0.6; <jats:italic>P<\/jats:italic> = 0.002). Subchondral bone fraction and osteophyte volume were decreased. However, cartilage explants from Col1a1\u2010Dkk\u20101\u2013Tg mice showed proteoglycan loss and increased NITEGE expression. Expression of vascular endothelial growth factor (VEGF) was reduced in osteoblasts from Col1a1\u2010Dkk\u20101\u2013Tg mice, thereby decreasing expression of messenger RNA for matrix metalloproteinases in chondrocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Wnt activation in OA affects the whole joint, particularly bone. Selective inhibition of this pathway in bone by Dkk\u20101 decreased OA severity through VEGF inhibition.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38799","type":"journal-article","created":{"date-parts":[[2014,7,30]],"date-time":"2014-07-30T10:56:06Z","timestamp":1406717766000},"page":"3028-3039","source":"Crossref","is-referenced-by-count":123,"title":["Dkk\u20101\u2013Mediated Inhibition of Wnt Signaling in Bone Ameliorates Osteoarthritis in Mice"],"prefix":"10.1002","volume":"66","author":[{"given":"Thomas","family":"Funck\u2010Brentano","sequence":"first","affiliation":[{"name":"INSERM UMR\u20101132, H\u00f4pital Lariboisi\u00e8re, and Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafa","family":"Bouaziz","sequence":"additional","affiliation":[{"name":"INSERM UMR\u20101132, H\u00f4pital Lariboisi\u00e8re, and Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Marty","sequence":"additional","affiliation":[{"name":"INSERM UMR\u20101132, H\u00f4pital Lariboisi\u00e8re, and Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Geoffroy","sequence":"additional","affiliation":[{"name":"INSERM UMR\u20101132, H\u00f4pital Lariboisi\u00e8re Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hay","sequence":"additional","affiliation":[{"name":"INSERM UMR\u20101132, H\u00f4pital Lariboisi\u00e8re, and Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Cohen\u2010Solal","sequence":"additional","affiliation":[{"name":"INSERM UMR\u20101132, H\u00f4pital Lariboisi\u00e8re, and Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2005.09.007"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2011.12.003"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.129"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60243-2"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2011.04.003"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33445"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.06.006"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033543"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2011.150243"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.178"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.25"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0270"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28551"},{"key":"e_1_2_6_15_1","unstructured":"The Wnt Homepage.2012. 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