{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:58:50Z","timestamp":1792292330582,"version":"4.4.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2017,12]]},"DOI":"10.1186\/s13075-017-1363-4","type":"journal-article","created":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T07:39:31Z","timestamp":1500968371000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Targeted designed variants of alpha-2-macroglobulin (A2M) attenuate cartilage degeneration in a rat model of osteoarthritis induced by anterior cruciate ligament transection"],"prefix":"10.1186","volume":"19","author":[{"given":"Yang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Browning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Scuderi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis S.","family":"Hanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,25]]},"reference":[{"issue":"6","key":"1363_CR1","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/jor.21359","volume":"29","author":"DD Anderson","year":"2011","unstructured":"Anderson DD, Chubinskaya S, Guilak F, Martin JA, Oegema TR, Olson SA, Buckwalter JA. Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J Orthop Res. 2011;29(6):802\u20139.","journal-title":"J Orthop Res"},{"issue":"4","key":"1363_CR2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00296-010-1592-1","volume":"31","author":"KS Kim","year":"2011","unstructured":"Kim KS, Choi HM, Lee Y-A, Choi IA, Lee S-H, Hong S-J, Yang H-I, Yoo MC. Expression levels and association of gelatinases MMP-2 and MMP-9 and collagenases MMP-1 and MMP-13 with VEGF in synovial fluid of patients with arthritis. Rheumatol Int. 2011;31(4):543\u20137.","journal-title":"Rheumatol Int"},{"issue":"2","key":"1363_CR3","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1302\/0301-620X.86B2.14474","volume":"86","author":"K Kanbe","year":"2004","unstructured":"Kanbe K, Takemura T, Takeuchi K, Chen Q, Takagishi K, Inoue K. Synovectomy reduces stromal-cell-derived factor-1 (SDF-1) which is involved in the destruction of cartilage in osteoarthritis and rheumatoid arthritis. J Bone Joint Surg Br. 2004;86(2):296\u2013300.","journal-title":"J Bone Joint Surg Br"},{"issue":"7","key":"1363_CR4","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/jor.21093","volume":"28","author":"L Wei","year":"2010","unstructured":"Wei L, Fleming BC, Sun X, Teeple E, Wu W, Jay GD, Elsaid KA, Luo J, Machan JT, Chen Q. Comparison of differential biomarkers of osteoarthritis with and without posttraumatic injury in the Hartley guinea pig model. J Orthop Res. 2010;28(7):900\u20136.","journal-title":"J Orthop Res"},{"issue":"7","key":"1363_CR5","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1002\/art.38576","volume":"66","author":"S Wang","year":"2014","unstructured":"Wang S, Wei X, Zhou J, Zhang J, Li K, Chen Q, Terek R, Fleming BC, Goldring MB, Ehrlich MG, et al. Identification of alpha2-macroglobulin as a master inhibitor of cartilage-degrading factors that attenuates the progression of posttraumatic osteoarthritis. Arthritis Rheumatol. 2014;66(7):1843\u201353.","journal-title":"Arthritis Rheumatol"},{"issue":"10","key":"1363_CR6","first-page":"2201","volume":"88","author":"DM Green","year":"2006","unstructured":"Green DM, Noble PC, Bocell Jr JR, Ahuero JS, Poteet BA, Birdsall HH. Effect of early full weight-bearing after joint injury on inflammation and cartilage degradation. J Bone Joint Surg Am. 2006;88(10):2201\u20139.","journal-title":"J Bone Joint Surg Am"},{"issue":"4","key":"1363_CR7","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/jor.21270","volume":"29","author":"JD Backus","year":"2011","unstructured":"Backus JD, Furman BD, Swimmer T, Kent CL, McNulty AL, Defrate LE, Guilak F, Olson SA. Cartilage viability and catabolism in the intact porcine knee following transarticular impact loading with and without articular fracture. J Orthop Res. 2011;29(4):501\u201310.","journal-title":"J Orthop Res"},{"issue":"9","key":"1363_CR8","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1097\/00005131-200310000-00006","volume":"17","author":"J Borrelli Jr","year":"2003","unstructured":"Borrelli Jr J, Tinsley K, Ricci WM, Burns M, Karl IE, Hotchkiss R. Induction of chondrocyte apoptosis following impact load. J Orthop Trauma. 2003;17(9):635\u201341.","journal-title":"J Orthop Trauma"},{"issue":"6","key":"1363_CR9","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2106\/JBJS.I.01777","volume":"93","author":"Y Tochigi","year":"2011","unstructured":"Tochigi Y, Buckwalter JA, Martin JA, Hillis SL, Zhang P, Vaseenon T, Lehman AD, Brown TD. Distribution and progression of chondrocyte damage in a whole-organ model of human ankle intra-articular fracture. J Bone Joint Surg Am. 2011;93(6):533\u20139.","journal-title":"J Bone Joint Surg Am"},{"issue":"7","key":"1363_CR10","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.joca.2012.03.010","volume":"20","author":"F Wei","year":"2012","unstructured":"Wei F, Zhou J, Wei X, Zhang J, Fleming BC, Terek R, Pei M, Chen Q, Liu T, Wei L. Activation of Indian hedgehog promotes chondrocyte hypertrophy and upregulation of MMP-13 in human osteoarthritic cartilage. Osteoarthr Cartil. 2012;20(7):755\u201363.","journal-title":"Osteoarthr Cartil"},{"issue":"4","key":"1363_CR11","doi-asserted-by":"crossref","first-page":"R177","DOI":"10.1186\/ar3930","volume":"14","author":"FMD Wei","year":"2012","unstructured":"Wei FMD, Li Y, Zhang G, Wei X, Lee JK, Wei L. Attenuation of osteoarthritis via blockade of the SDF-1\/CXCR4 signaling pathway. Arthritis Res Ther. 2012;14(4):R177. [Epub ahead of print](PMCID:PMC3580571).","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"1363_CR12","doi-asserted-by":"crossref","first-page":"R11","DOI":"10.1186\/ar4437","volume":"16","author":"J Zhou","year":"2014","unstructured":"Zhou J, Chen Q, Lanske B, Fleming BC, Terek R, Wei X, Zhang G, Wang S, Li K, Wei L. Disrupting the Indian hedgehog signaling pathway in vivo attenuates surgically induced osteoarthritis progression in Col2a1-CreERT2; Ihhfl\/fl mice. Arthritis Res Ther. 2014;16(1):R11.","journal-title":"Arthritis Res Ther"},{"issue":"4","key":"1363_CR13","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1002\/art.33461","volume":"64","author":"GD Jay","year":"2012","unstructured":"Jay GD, Elsaid KA, Kelly KA, Anderson SC, Zhang L, Teeple E, Waller K, Fleming BC. Prevention of cartilage degeneration and gait asymmetry by lubricin tribosupplementation in the rat following anterior cruciate ligament transection. Arthritis Rheum. 2012;64(4):1162\u201371.","journal-title":"Arthritis Rheum"},{"key":"1363_CR14","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0076-6879(93)23041-K","volume":"223","author":"G Salvesen","year":"1993","unstructured":"Salvesen G, Enghild JJ. alpha-Macroglobulins: detection and characterization. Methods Enzymol. 1993;223:121\u201341.","journal-title":"Methods Enzymol"},{"issue":"1","key":"1363_CR15","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/03008200490278115","volume":"45","author":"B Demirag","year":"2004","unstructured":"Demirag B, Sarisozen B, Durak K, Bilgen OF, Ozturk C. The effect of alpha-2 macroglobulin on the healing of ruptured anterior cruciate ligament in rabbits. Connect Tissue Res. 2004;45(1):23\u20137.","journal-title":"Connect Tissue Res"},{"issue":"11","key":"1363_CR16","first-page":"2401","volume":"87","author":"B Demirag","year":"2005","unstructured":"Demirag B, Sarisozen B, Ozer O, Kaplan T, Ozturk C. Enhancement of tendon-bone healing of anterior cruciate ligament grafts by blockage of matrix metalloproteinases. J Bone Joint Surg Am. 2005;87(11):2401\u201310.","journal-title":"J Bone Joint Surg Am"},{"issue":"3","key":"1363_CR17","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1177\/0363546515621285","volume":"44","author":"G Du","year":"2016","unstructured":"Du G, Zhan H, Ding D, Wang S, Wei X, Wei F, Zhang J, Bilgen B, Reginato AM, Fleming BC, et al. Abnormal mechanical loading induces cartilage degeneration by accelerating meniscus hypertrophy and mineralization after ACL injuries in vivo. Am J Sports Med. 2016;44(3):652\u201363.","journal-title":"Am J Sports Med"},{"issue":"8","key":"1363_CR18","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1002\/art.27550","volume":"62","author":"GD Jay","year":"2010","unstructured":"Jay GD, Fleming BC, Watkins BA, McHugh KA, Anderson SC, Zhang LX, Teeple E, Waller KA, Elsaid KA. Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transection. Arthritis Rheum. 2010;62(8):2382\u201391.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"1363_CR19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","volume":"14","author":"KPH Pritzker","year":"2006","unstructured":"Pritzker KPH, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D, van den Berg WB. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthr Cartil. 2006;14(1):13\u201329.","journal-title":"Osteoarthr Cartil"},{"issue":"Suppl 3","key":"1363_CR20","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1016\/j.joca.2010.05.030","volume":"18","author":"N Gerwin","year":"2010","unstructured":"Gerwin N, Bendele AM, Glasson S, Carlson CS. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat. Osteoarthr Cartil. 2010;18 Suppl 3:S24\u201334.","journal-title":"Osteoarthr Cartil"},{"issue":"17","key":"1363_CR21","doi-asserted-by":"crossref","first-page":"17554","DOI":"10.1074\/jbc.M313041200","volume":"279","author":"MD Tortorella","year":"2004","unstructured":"Tortorella MD, Arner EC, Hills R, Easton A, Korte-Sarfaty J, Fok K, Wittwer AJ, Liu R-Q, Malfait A-M. Alpha2-macroglobulin is a novel substrate for ADAMTS-4 and ADAMTS-5 and represents an endogenous inhibitor of these enzymes. J Biol Chem. 2004;279(17):17554\u201361.","journal-title":"J Biol Chem"},{"issue":"11","key":"1363_CR22","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.joca.2008.03.017","volume":"16","author":"Y Luan","year":"2008","unstructured":"Luan Y, Kong L, Howell DR, Ilalov K, Fajardo M, Bai XH, Di Cesare PE, Goldring MB, Abramson SB, Liu CJ. Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin. Osteoarthr Cartil. 2008;16(11):1413\u201320.","journal-title":"Osteoarthr Cartil"},{"issue":"9","key":"1363_CR23","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1002\/art.1780340910","volume":"34","author":"JJ Abbink","year":"1991","unstructured":"Abbink JJ, Kamp AM, Nieuwenhuys EJ, Nuijens JH, Swaak AJ, Hack CE. Predominant role of neutrophils in the inactivation of alpha 2-macroglobulin in arthritic joints. Arthritis Rheum. 1991;34(9):1139\u201350.","journal-title":"Arthritis Rheum"},{"issue":"3","key":"1363_CR24","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3109\/03008200903288902","volume":"51","author":"L Zhang","year":"2010","unstructured":"Zhang L, Yang M, Yang D, Cavey G, Davidson P, Gibson G. Molecular interactions of MMP-13 C-terminal domain with chondrocyte proteins. Connect Tissue Res. 2010;51(3):230\u20139.","journal-title":"Connect Tissue Res"},{"issue":"1","key":"1363_CR25","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1055\/s-0038-1647450","volume":"65","author":"JJ Abbink","year":"1991","unstructured":"Abbink JJ, Nuijens JH, Eerenberg AJ, Huijbregts CC, van Schijndel RJS, Thijs LG, Hack CE. Quantification of functional and inactivated alpha 2-macroglobulin in sepsis. Thromb Haemost. 1991;65(1):32\u20139.","journal-title":"Thromb Haemost"},{"issue":"1","key":"1363_CR26","first-page":"3","volume":"65","author":"J LaMarre","year":"1991","unstructured":"LaMarre J, Wollenberg GK, Gonias SL, Hayes MA. Cytokine binding and clearance properties of proteinase-activated alpha 2-macroglobulins. Lab Investig. 1991;65(1):3\u201314.","journal-title":"Lab Investig"},{"issue":"2","key":"1363_CR27","first-page":"265","volume":"138","author":"GK Wollenberg","year":"1991","unstructured":"Wollenberg GK, LaMarre J, Rosendal S, Gonias SL, Hayes MA. Binding of tumor necrosis factor alpha to activated forms of human plasma alpha 2 macroglobulin. Am J Pathol. 1991;138(2):265\u201372.","journal-title":"Am J Pathol"},{"issue":"11","key":"1363_CR28","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.4049\/jimmunol.145.11.3747","volume":"145","author":"W Borth","year":"1990","unstructured":"Borth W, Scheer B, Urbansky A, Luger TA, Sottrup-Jensen L. Binding of IL-1 beta to alpha-macroglobulins and release by thioredoxin. J Immunol. 1990;145(11):3747\u201354.","journal-title":"J Immunol"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-017-1363-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T13:56:54Z","timestamp":1692885414000},"score":1,"resource":{"primary":{"URL":"http:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-017-1363-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,25]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["1363"],"URL":"https:\/\/doi.org\/10.1186\/s13075-017-1363-4","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,25]]},"article-number":"175"}}