{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T03:06:12Z","timestamp":1767927972576,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2004,8,5]],"date-time":"2004-08-05T00:00:00Z","timestamp":1091664000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the importance of the enzymatic activity of ADAMTS\u20104 in normal growth and development and to evaluate the role of ADAMTS\u20104 in the progression of osteoarthritis (OA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated catalytic domain\u2013deleted ADAMTS\u20104\u2013transgenic mice and performed extensive gross and histologic analyses of various organs. The mice were challenged by surgical induction of joint instability leading to OA, to determine the importance of the enzymatic activity of ADAMTS\u20104 in the progression of the disease. The response of wild\u2010type (WT) and ADAMTS\u20104\u2013knockout (ADAMTS\u20104\u2013KO) articular cartilage to interleukin\u20101 and retinoic acid challenge in vitro was also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ADAMTS\u20104\u2013KO mice up to 1 year of age exhibited no gross or histologic abnormalities in 36 tissue sites examined. Despite evidence of ADAMTS\u20104 expression and activity in growth plates of WT mice, catalytic silencing of this proteinase caused no abnormalities in skeletal development, growth, or remodeling. There was no effect of ADAMTS\u20104 knockout on the progression or severity of OA 4 weeks or 8 weeks after surgical induction of joint instability. Enzymatic cleavage of aggrecan at the TEGE<jats:sup>373\u2013374<\/jats:sup>ARGS site was clearly evident after exposure of articular cartilage from ADAMTS\u20104\u2013KO mice to inflammatory cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although expression of the ADAMTS\u20104 gene has been found in many tissues throughout the body, deletion of enzymatic activity did not appear to have any effect on normal growth and physiology. Our study provides evidence that ADAMTS\u20104 is the primary aggrecanase in murine growth plates; however, deletion of its enzymatic activity did not affect normal long bone remodeling. Our results also lead to the hypothesis that, in the mouse, ADAMTS\u20104 is not the primary enzyme responsible for aggrecan degradation at the TEGE<jats:sup>373\u2013374<\/jats:sup>ARGS site. The elucidation of the relative importance of ADAMTS\u20104 in the pathologic process of human OA will require examination of human OA tissues and evidence of disease modification in patients following therapeutic intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20558","type":"journal-article","created":{"date-parts":[[2004,8,9]],"date-time":"2004-08-09T20:05:15Z","timestamp":1092081915000},"page":"2547-2558","source":"Crossref","is-referenced-by-count":240,"title":["Characterization of and osteoarthritis susceptibility in ADAMTS\u20104\u2013knockout mice"],"prefix":"10.1002","volume":"50","author":[{"given":"Sonya S.","family":"Glasson","sequence":"first","affiliation":[]},{"given":"Roger","family":"Askew","sequence":"additional","affiliation":[]},{"given":"Barbara","family":"Sheppard","sequence":"additional","affiliation":[]},{"given":"Brenda A.","family":"Carito","sequence":"additional","affiliation":[]},{"given":"Tracey","family":"Blanchet","sequence":"additional","affiliation":[]},{"given":"Hak\u2010Ling","family":"Ma","sequence":"additional","affiliation":[]},{"given":"Carl R.","family":"Flannery","sequence":"additional","affiliation":[]},{"given":"Kim","family":"Kanki","sequence":"additional","affiliation":[]},{"given":"Eunice","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Diane","family":"Peluso","sequence":"additional","affiliation":[]},{"given":"Zhiyong","family":"Yang","sequence":"additional","affiliation":[]},{"given":"Manas K.","family":"Majumdar","sequence":"additional","affiliation":[]},{"given":"Elisabeth A.","family":"Morris","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2004,8,5]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(01)00055-8"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360906"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5420.1664"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.23443"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10531"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.2.721"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2001.0427"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200201)46:1<124::AID-ART10121>3.0.CO;2-X"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.3.1405"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M909383199"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(02)00069-0"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M909764199"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009737200"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81169-1"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0934-8832(11)80072-7"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.1168"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200106)44:6<1455::AID-ART241>3.0.CO;2-J"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(86)90306-5"},{"key":"e_1_2_6_20_2","article-title":"ADAMTS8 exhibits aggrecanase activity and is expressed in human articular cartilage","author":"Collins\u2010Racie LA","journal-title":"Matrix Biol."},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200431200"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.36.22389"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5437.113"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.9.3942"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.140.6.1535"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80064-1"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199801)41:1<110::AID-ART14>3.0.CO;2-G"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11355"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8635"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/90100"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.2002"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni773"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2380571"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0934-8832(11)80223-4"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3620473"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keg109"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11323"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M910207199"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.37.23959"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007674200"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01854-8"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00254-1"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211009200"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.20558","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.20558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T23:37:22Z","timestamp":1696981042000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.20558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8]]},"references-count":42,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2004,8]]}},"alternative-id":["10.1002\/art.20558"],"URL":"https:\/\/doi.org\/10.1002\/art.20558","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8]]}}}