{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T10:13:05Z","timestamp":1774260785002,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,4,7]],"date-time":"2005-04-07T00:00:00Z","timestamp":1112832000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Interdisciplinary Clinical Research Center at the Medical Faculty of the Friedrich-Alexander-University Erlangen-Nuremberg","award":["C3"],"award-info":[{"award-number":["C3"]}]},{"name":"Interdisciplinary Clinical Research Center at the Medical Faculty of the Friedrich-Alexander-University Erlangen-Nuremberg","award":["C4"],"award-info":[{"award-number":["C4"]}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","award":["01 KS 0002"],"award-info":[{"award-number":["01 KS 0002"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The membrane\u2010anchored metalloproteinase disintegrin ADAM15 is up\u2010regulated in osteoarthritis and has been implicated in proteolysis and cell\u2013matrix interactions. To address its role in cartilage metabolism, we performed an analysis of joint morphology in aging mice with a targeted inactivation of the ADAM15 gene (ADAM15<jats:sup>\u2212\/\u2212<\/jats:sup>). In addition, a human chondrocyte cell line overexpressing ADAM15 was used to investigate the role of ADAM15 in an in vitro model of chondrocyte\u2013matrix interactions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Knee joint sections from 3\u2010, 6\u2010, and 12\u201314\u2010month\u2010old ADAM15<jats:sup>\u2212\/\u2212<\/jats:sup> and wild\u2010type (WT) 129\/SvJ mice were examined for synovial hyperplasia, cartilage degradation, and osteophyte formation. Stable transfection of the human T\/C28a4 chondrocyte cell line with full\u2010length human ADAM15 complementary DNA led to the establishment of ADAM15\u2010overexpressing chondrocytes that were further analyzed for their capability to adhere to and to survive on cartilage matrix molecules (fibronectin and types II and VI collagen) under conditions of serum starvation. ADAM15 expression was investigated by reverse transcription\u2013polymerase chain reaction and Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Aging ADAM15<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited accelerated development of osteoarthritic lesions compared with WT mice, and the difference was statistically significant at age 12 months. The osteoarthritic changes preferentially affected male ADAM15<jats:sup>\u2212\/\u2212<\/jats:sup> mice. ADAM15 overexpression in T\/C28a4 cells led to the specific reinforcement of chondrocyte adhesion to cartilage types II and VI collagen, and this was associated with enhanced cell viability under conditions of serum starvation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The accelerated development of murine osteoarthritis in ADAM15 deficiency as well as the proadhesive and cell survival\u2013promoting in vitro effect of ADAM15 overexpression suggest a homeostatic rather than a destructive role of ADAM15 in cartilage remodeling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20974","type":"journal-article","created":{"date-parts":[[2005,4,7]],"date-time":"2005-04-07T15:18:14Z","timestamp":1112887094000},"page":"1100-1109","source":"Crossref","is-referenced-by-count":54,"title":["Homeostatic effects of the metalloproteinase disintegrin ADAM15 in degenerative cartilage remodeling"],"prefix":"10.1002","volume":"52","author":[{"given":"Beate B.","family":"B\u00f6hm","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Aigner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Brodie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl P.","family":"Blobel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Burkhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,4,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1548"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1039703"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001953200"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.4.1457"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.5.1143"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208937200"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.13.7345"},{"key":"e_1_2_6_9_2","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1242\/jcs.112.4.579","article-title":"Interaction of metargidin (ADAM\u201015) with \u03b1v\u03b23 and \u03b15\u03b21 integrins on different haemopoietic cells","volume":"112","author":"Nath D","year":"1999","journal-title":"J Cell Sci"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2002.5606"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M213157200"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107430200"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.44.31693"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.16.5614-5624.2003"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199909)42:9<1946::AID-ANR21>3.0.CO;2-E"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200109)44:9<2046::AID-ART354>3.0.CO;2-3"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117595"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(91)90198-O"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20034"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.1999.0277"},{"key":"e_1_2_6_21_2","first-page":"109","article-title":"Chondrocyte integrin expression and function","volume":"37","author":"Loeser RF","year":"2000","journal-title":"Biorheology"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0029(19981015)43:2<111::AID-JEMT4>3.0.CO;2-O"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(99)00027-X"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11246"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.2.587"}],"container-title":["Arthritis &amp; 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