{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:55:28Z","timestamp":1791258928510,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,12,13]],"date-time":"2005-12-13T00:00:00Z","timestamp":1134432000000},"content-version":"vor","delay-in-days":4486,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatism"],"published-print":{"date-parts":[[1993,9]]},"abstract":"Abstract<\/jats:title>Objective.<\/jats:italic> To determine the proteolytic fragmentation patterns and N\u2010terminal sequence of aggrecan fragments in human synovial fluid from patients with inflammatory arthritides, joint injury, or osteoarthritis (OA).<\/jats:p>Methods.<\/jats:italic> Knee synovial fluid was obtained from patients with joint injury, OA, acute pyrophosphate arthritis (pseudogout), reactive arthritis, psoriatic arthritis, or juvenile rheumatoid arthritis. Chondroitin sulfate\u2013substituted aggrecan fragments present in the fluid were purified by cesium chloride gradient centrifugation and enzymatically deglycosylated. Core protein species were determined by N\u2010terminal analysis and by sodium dodecyl sulfate\u2013polyacrylamide gel electrophoresis (SDS\u2010PAGE) with electroblotting and detection with monoclonal antibody 3B3.<\/jats:p>Results.<\/jats:italic> Samples from patients with joint injury, OA, and inflammatory joint disease all showed a similar 3\u2010band pattern, with core sizes of approximately 200 kd, 170 kd, and 135 kd. In all samples, diffuse immuno\u2010reactive products were also seen, with an apparent size of >250 kd. N\u2010terminal analysis of core preparations of all samples showed a consistent single predominant sequence, beginning at alanine 374 of the human aggrecan core protein.<\/jats:p>Conclusion.<\/jats:italic> The aggrecan fragments present in joint fluids from patients with various inflammatory arthritides, joint injury, or OA result from a predominant cleavage of the human aggrecan core protein at the glutamate 373\u2013alanine 374 bond within the interglobular domain, between the G1 and G2 domains. The consistent pattern of fragments seen on SDS\u2010PAGE and the single predominant N\u2010terminal sequence suggest a common degradative mechanism of aggrecan in these different joint conditions. The identity of the proteolytic agent (aggrecanase), however, remains unknown. These results appear to have important implications with regard to the development of therapies to protect cartilage from degradation in patients with joint disease.<\/jats:p>","DOI":"10.1002\/art.1780360906","type":"journal-article","created":{"date-parts":[[2007,2,15]],"date-time":"2007-02-15T01:08:23Z","timestamp":1171501703000},"page":"1214-1222","source":"Crossref","is-referenced-by-count":322,"title":["The structure of aggrecan fragments in human synovial fluid. evidence that aggrecanase mediates cartilage degradation in inflammatory joint disease, joint injury, and osteoarthritis"],"prefix":"10.1002","volume":"36","author":[{"given":"L.","family":"Stefan Lohmander","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Neame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Sandy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,13]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1930193"},{"key":"e_1_2_1_3_2","first-page":"17238","article-title":"Discoordinate expression of stromelysin, collagenase, and TIMP\u2010I in rheumatoid synovial fibroblasts","volume":"265","author":"MacNaul KL","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0180812"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114215"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780340903"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780340904"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350106"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360207"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780330516"},{"key":"e_1_2_1_11_2","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1042\/bj2850857","article-title":"Characterization of proteoglycan degradation by calpain","volume":"285","author":"Suzuki K","year":"1992","journal-title":"Biochem J"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2870657"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(88)90008-6"},{"key":"e_1_2_1_14_2","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S0021-9258(17)35257-2","article-title":"Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan","volume":"266","author":"Doege K","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115742"},{"key":"e_1_2_1_16_2","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/S0021-9258(18)48387-1","article-title":"Identification of a stromelysin cleavage site within the interglobular domain of human aggrecan: evidence for proteolysis at this site in vivo in human articular cartilage","volume":"267","author":"Flannery CR","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_1_17_2","doi-asserted-by":"crossref","first-page":"19470","DOI":"10.1016\/S0021-9258(18)41799-1","article-title":"The interglobular domain of cartilage aggrecan is cleaved by PUMP, gelatinases and cathepsin B","volume":"267","author":"Fosang AJ","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_2_1_18_2","unstructured":"FlanneryCR SandyJD: Aggrecan catabolism in cartilage: studies on the nature of a novel proteinase (aggrecanase) which cleaves the Glu\u2010373\u2010Ala 374 bond of the interglobular domain (abstract). 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