{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:56:50Z","timestamp":1791262610091,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T00:00:00Z","timestamp":1343347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Dkk is a family of canonical Wnt antagonists with 4 members (Dkk\u20101, Dkk\u20102, Dkk\u20103, and Dkk\u20104). We undertook this study to explore the roles of Dkk\u20101 and Dkk\u20102 in osteoarthritic (OA) cartilage destruction in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Expression of Dkk and other catabolic factors was determined at the messenger RNA and protein levels in human and mouse OA cartilage. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) or by intraarticular injection of <jats:italic>Epas1<\/jats:italic> adenovirus (AdEPAS\u20101). The role of Dkk in OA pathogenesis was examined by intraarticular injection of AdDkk\u20101 or by using chondrocyte\u2010specific <jats:italic>Dkk1<\/jats:italic> (<jats:italic>Col2a1\u2010Dkk1<\/jats:italic>)\u2013transgenic mice and <jats:italic>Dkk2<\/jats:italic> (<jats:italic>Col2a1\u2010Dkk2<\/jats:italic>)\u2013transgenic mice. Primary culture mouse chondrocytes were also treated with recombinant Dkk proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found opposite patterns of <jats:italic>Dkk1<\/jats:italic> and <jats:italic>Dkk2<\/jats:italic> expression in human and mouse experimental OA cartilage: <jats:italic>Dkk1<\/jats:italic> was up\u2010regulated and <jats:italic>Dkk2<\/jats:italic> was down\u2010regulated. Overexpression of <jats:italic>Dkk1<\/jats:italic> by intraarticular injection of AdDkk\u20101 significantly inhibited DMM\u2010induced experimental OA. DMM\u2010induced OA was also significantly inhibited in <jats:italic>Col2a1\u2010Dkk1<\/jats:italic>\u2013transgenic mice compared with their wild\u2010type littermates. However, <jats:italic>Col2a1\u2010Dkk2<\/jats:italic>\u2013transgenic mice showed no significant difference in OA pathogenesis. Wnt\u20103a, which activates the canonical Wnt pathway, induced <jats:italic>Mmp13<\/jats:italic> and <jats:italic>Adamts4<\/jats:italic> expression in primary culture chondrocytes, an effect that was significantly inhibited by Dkk\u20101 pretreatment or <jats:italic>Dkk1<\/jats:italic> overexpression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that expression of <jats:italic>Dkk1<\/jats:italic>, but not <jats:italic>Dkk2<\/jats:italic>, in chondrocytes inhibits OA cartilage destruction. The protective effect of Dkk\u20101 appears to be associated with its capacity to inhibit Wnt\u2010mediated expression of catabolic factors, such as <jats:italic>Mmp13<\/jats:italic>, providing evidence that Dkk\u20101 might serve as a therapeutic target for OA treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34481","type":"journal-article","created":{"date-parts":[[2012,4,5]],"date-time":"2012-04-05T17:10:39Z","timestamp":1333645839000},"page":"2568-2578","source":"Crossref","is-referenced-by-count":117,"title":["Dkk\u20101 expression in chondrocytes inhibits experimental osteoarthritic cartilage destruction in mice"],"prefix":"10.1002","volume":"64","author":[{"given":"Hwanhee","family":"Oh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Churl\u2010Hong","family":"Chun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang\u2010Soo","family":"Chun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,7,27]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21258"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.20113"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0904"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945010791011901"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23614"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080901"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.026096"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403456101"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20993"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23137"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210054"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.358"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00868-X"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(02)01106-X"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22867"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.102350"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-11-257"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.12.008"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.27357"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(01)00041-7"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2153"},{"issue":"2","key":"e_1_2_6_23_2","first-page":"1","article-title":"Histological assessment of cartilage repair: a report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS)","volume":"85","author":"Mainil\u2010Varlet P","year":"2003","journal-title":"J Bone Joint Surg Am"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.06.008"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2000.0363"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.03.006"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-197153030-00009"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.05.025"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.30451"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.25002"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02489045"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700965200"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.218065"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22334"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1538"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1583"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.111"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23444"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24247"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.07.004"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700747"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20558"}],"container-title":["Arthritis &amp; 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