{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:00:33Z","timestamp":1772118033464,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T00:00:00Z","timestamp":1382918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      We previously described a messenger RNA variant of\n                      <jats:italic>ADAMTS4<\/jats:italic>\n                      (\n                      <jats:italic>ADAMTS4_v1<\/jats:italic>\n                      ) in human synovial cell cocultures obtained from patients with osteoarthritis (OA). This RNA message has been found only in OA synovium and, if translated, would result in a protein identical to ADAMTS\u20104, except that the C\u2010terminal spacer domain would be different. The purpose of this study was to determine whether\n                      <jats:italic>ADAMTS4_v1<\/jats:italic>\n                      is translated into a protein, is expressed in vivo, and acts as a functional aggrecanase.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Polyclonal antibodies were raised against unique C\u2010terminal sequences of ADAMTS\u20104_v1. An immunohistochemical study of human OA synovium was performed. A mammalian expression vector coding for FLAG\u2010tagged human\n                      <jats:italic>ADAMTS4<\/jats:italic>\n                      was mutated to contain the different sequences of\n                      <jats:italic>ADAMTS4_v1<\/jats:italic>\n                      , and the resultant plasmid was used to transfect HEK 293 cells. ADAMTS\u20104_v1 produced by these cells was purified via the FLAG epitope, and the ability of this recombinant protein to cleave aggrecan, biglycan, and decorin was investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      An antibody specific for ADAMTS\u20104_v1 was found to bind to the synovial membrane surface on cryosections, and the protein was detected in cell lysates from synovium obtained from OA patients. The recombinant ADAMTS\u20104_v1 demonstrated enzyme activity toward the target substrate in a commercial aggrecanase 1 enzyme\u2010linked immunosorbent assay and was also found to cleave aggrecan at the pathologically important Glu\n                      <jats:sup>373\u2193374<\/jats:sup>\n                      Ala aggrecanase site.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ADAMTS\u20104_v1 is expressed as a protein in vivo in human OA synovium, functions as an aggrecanase, and cleaves other proteoglycan substrates. This splice variant may be a major contributor to loss of aggrecan from the superficial zone of OA cartilage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.38102","type":"journal-article","created":{"date-parts":[[2013,7,29]],"date-time":"2013-07-29T10:51:23Z","timestamp":1375095083000},"page":"2866-2875","source":"Crossref","is-referenced-by-count":11,"title":["ADAMTS\u20104_v1 Is a Splice Variant of ADAMTS\u20104 That Is Expressed as a Protein in Human Synovium and Cleaves Aggrecan at the Interglobular Domain"],"prefix":"10.1002","volume":"65","author":[{"given":"Shane D.","family":"Wainwright","sequence":"first","affiliation":[{"name":"Cardiff University Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Bondeson","sequence":"additional","affiliation":[{"name":"Cardiff University Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Caterson","sequence":"additional","affiliation":[{"name":"Cardiff University Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare E.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Cardiff University Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,10,28]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"222","article-title":"Osteoarthritis in 2007","volume":"65","author":"Krasnokutsky S","year":"2007","journal-title":"Bull NYU Hosp Jt Dis"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200106)44:6<1237::AID-ART214>3.0.CO;2-F"},{"key":"e_1_2_6_4_1","first-page":"698","article-title":"Arthroscopic evaluation of chondropathy in osteoarthritis of the knee","volume":"3","author":"Ayral X","year":"1996","journal-title":"J Rheumatol"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.025270"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2001.01990.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2013"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27290"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.06.014"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03369"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03417"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22334"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2006.03.006"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)02024-2"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel078"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3050799"},{"key":"e_1_2_6_17_1","first-page":"277","volume-title":"Extracellular matrix biochemistry","author":"Heinegard D","year":"1984"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3500181"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42759-7"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2005.09.018"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205309200"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107443200"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001065200"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20030896"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003875200"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.05.014"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312123200"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-9639(02)00532-0"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.07.012"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312100200"},{"key":"e_1_2_6_31_1","series-title":"Bone and osteoarthritis","first-page":"65","author":"Blom AB","year":"2007"}],"container-title":["Arthritis &amp; 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