{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:02:57Z","timestamp":1792782177029,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,6,27]],"date-time":"2014-06-27T00:00:00Z","timestamp":1403827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000964","name":"arthritis national research foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000964","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81071495"],"award-info":[{"award-number":["81071495"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81171676"],"award-info":[{"award-number":["81171676"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81201435"],"award-info":[{"award-number":["81201435"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH\/NCRR","award":["P20RR024484"],"award-info":[{"award-number":["P20RR024484"]}]},{"name":"NIH\/NIAMS","award":["R01AR059142"],"award-info":[{"award-number":["R01AR059142"]}]},{"name":"Shanxi Natural Science Foundation of China","award":["2011011042"],"award-info":[{"award-number":["2011011042"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2014,7]]},"abstract":"\n Objective<\/jats:title>\n \n To determine if supplemental intraarticular \u03b1\n 2<\/jats:sub>\n \u2010macroglobulin (\u03b1\n 2<\/jats:sub>\n M) has a chondroprotective effect in a rat model of osteoarthritis (OA).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Using Western blotting, mass spectrometry, enzyme\u2010linked immunosorbent assay (ELISA), and immunohistochemistry, \u03b1\n 2<\/jats:sub>\n M was identified as a potential therapeutic agent through a comparison of \u03b1\n 2<\/jats:sub>\n M concentrations in serum, synovial fluid (SF), and cartilage from normal subjects and patients with OA. In cultured chondrocytes, the effects of \u03b1\n 2<\/jats:sub>\n M on interleukin\u20101 (IL\u20101)\u2013induced cartilage catabolic enzymes were evaluated by Luminex assay and ELISA. In vivo effects on cartilage degeneration and matrix metalloproteinase 13 (MMP\u201013) concentration were evaluated in male rats (n = 120) randomized to 1 of 4 treatments: 1) anterior cruciate ligament transection (ACLT) and saline injections, 2) ACLT and 1 IU\/kg injections of \u03b1\n 2<\/jats:sub>\n M, 3) ACLT and 2 IU\/kg injections of \u03b1\n 2<\/jats:sub>\n M, or 4) sham operation and saline injections. Rats were administered intraarticular injections for 6 weeks. The concentration of MMP\u201013 in SF lavage fluid was measured using ELISA. OA\u2010related gene expression was quantified by real\u2010time quantitative polymerase chain reaction. The extent of OA progression was graded by histologic examination.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In both normal subjects and OA patients, \u03b1\n 2<\/jats:sub>\n M levels were lower in SF as compared to serum, and in OA patients, MMP\u201013 levels were higher in SF than in serum. In vitro, \u03b1\n 2<\/jats:sub>\n M inhibited the induction of MMP\u201013 by IL\u20101 in a dose\u2010dependent manner in human chondrocytes. In the rat model of ACLT OA, supplemental intraarticular injection of \u03b1\n 2<\/jats:sub>\n M reduced the concentration of MMP\u201013 in SF, had a favorable effect on OA\u2010related gene expression, and attenuated OA progression.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The plasma protease inhibitor \u03b1\n 2<\/jats:sub>\n M is not present in sufficient concentrations to inactivate the high concentrations of catabolic factors found in OA SF. Our findings suggest that supplemental intraarticular \u03b1\n 2<\/jats:sub>\n M provides chondral protection in posttraumatic OA.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.38576","type":"journal-article","created":{"date-parts":[[2014,2,27]],"date-time":"2014-02-27T10:57:24Z","timestamp":1393498644000},"page":"1843-1853","source":"Crossref","is-referenced-by-count":92,"title":["Identification of \u03b1\n 2<\/sub>\n \u2010Macroglobulin as a Master Inhibitor of Cartilage\u2010Degrading Factors That Attenuates the Progression of Posttraumatic Osteoarthritis"],"prefix":"10.1002","volume":"66","author":[{"given":"Shaowei","family":"Wang","sequence":"first","affiliation":[{"name":"Warren Alpert Medical School of Brown University and Rhode Island Hospital Providence Rhode Island"},{"name":"The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China, and Zhejiang University School of Medicine Hangzhou, Zhejiang 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