{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T11:18:52Z","timestamp":1793013532057,"version":"4.5.0"},"reference-count":61,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2015,8,26]],"date-time":"2015-08-26T00:00:00Z","timestamp":1440547200000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR050180"],"award-info":[{"award-number":["AR050180"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F32 AR061186"],"award-info":[{"award-number":["F32 AR061186"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR054099"],"award-info":[{"award-number":["AR054099"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004209","name":"Otto M\u00f8nsteds Fond","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100004209","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Knud H\u00f8jgaards Fond","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Synovial fluid in an articulating joint contains proteins derived from the blood plasma and proteins that are produced by cells within the joint tissues, such as synovium, cartilage, ligament, and meniscus. The proteome composition of healthy synovial fluid and the cellular origins of many synovial fluid components are not fully understood. Here, we present a normative proteomics study using porcine synovial fluid. Using our optimized method, we identified 267 proteins with high confidence in healthy synovial fluid. We also evaluated mRNA expression data from tissues that can contribute to the synovial fluid proteome, including synovium, cartilage, blood, and liver, to better estimate the relative contributions from these sources to specific synovial fluid components. We identified 113 proteins in healthy synovial fluid that appear to be primarily derived from plasma transudates, 37 proteins primarily derived from synovium, and 11 proteins primarily derived from cartilage. Finally, we compared the identified synovial fluid proteome to the proteome of human plasma, and we found that the two body fluids share many similarities, underlining the detected plasma derived nature of many synovial fluid components. Knowing the synovial fluid proteome of a healthy joint will help to identify mechanisms that cause joint disease and pathways involved in disease progression.<\/jats:p>","DOI":"10.1021\/pr500587x","type":"journal-article","created":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T21:26:34Z","timestamp":1409088394000},"page":"4377-4387","source":"Crossref","is-referenced-by-count":89,"title":["A Normative Study of the Synovial\nFluid Proteome from\nHealthy Porcine Knee Joints"],"prefix":"10.1021","volume":"13","author":[{"given":"Tue","family":"Bennike","sequence":"first","affiliation":[{"name":"Boston Children\u2019s Hospital , , , , ,","place":["Boston, Massachusetts, United States, 02115"]},{"name":"Aalborg University , , ,","place":["Aalborg, Denmark, DK-9220"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugur","family":"Ayturk","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital , , , , ,","place":["Boston, Massachusetts, United States, 02115"]},{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla M.","family":"Haslauer","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital , , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Froehlich","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital , , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt L.","family":"Proffen","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital , , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Barnaby","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital , , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svend","family":"Birkelund","sequence":"additional","affiliation":[{"name":"Aalborg University , , ,","place":["Aalborg, Denmark, DK-9220"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha M.","family":"Murray","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital , , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"Warman","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital , , , , ,","place":["Boston, Massachusetts, United States, 02115"]},{"name":"Boston Children\u2019s Hospital , , , , ,","place":["Boston, Massachusetts, United States, 02115"]},{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Stensballe","sequence":"additional","affiliation":[{"name":"Aalborg University , , ,","place":["Aalborg, Denmark, DK-9220"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanno","family":"Steen","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital , , , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,8,26]]},"reference":[{"key":"2026090116331622900_cit1","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1016\/j.jprot.2011.12.042","article-title":"Differential protein profiling of synovial fluid from\nrheumatoid arthritis and osteoarthritis patients using LC\u2013MALDI\nTOF\/TOF","volume":"75","author":"Mateos","year":"2012","journal-title":"J. Proteomics"},{"key":"2026090116331622900_cit2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/art.1780240104","article-title":"The lubricating\nactivity of synovial fluid glycoproteins","volume":"24","author":"Swann","year":"1981","journal-title":"Arthritis\nRheum."},{"key":"2026090116331622900_cit3","first-page":"15","article-title":"A systems biology approach to synovial\njoint lubrication\nin health, injury, and disease","volume":"4","author":"Hui","year":"2012","journal-title":"Wiley Interdiscip.\nRev.: Syst. Biol. Med."},{"key":"2026090116331622900_cit4","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1172\/JCI103657","article-title":"Characterization of the proteins of certain postmortem\nhuman synovial fluids","volume":"37","author":"Schmid","year":"1958","journal-title":"J. Clin. Invest."},{"key":"2026090116331622900_cit5","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1172\/JCI103334","article-title":"Characterization\nof the proteins of human synovial\nfluid in certain disease states","volume":"35","author":"Schmid","year":"1956","journal-title":"J. Clin. Invest."},{"key":"2026090116331622900_cit6","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.talanta.2009.05.022","article-title":"Strategies to optimize\ntwo-dimensional gel electrophoresis\nanalysis of the human joint proteome","volume":"80","author":"Ruiz-Romero","year":"2010","journal-title":"Talanta"},{"key":"2026090116331622900_cit7","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1172\/JCI101182","article-title":"The origin and nature of normal human\nsynovial fluid","volume":"19","author":"Ropes","year":"1940","journal-title":"J. Clin. Invest."},{"key":"2026090116331622900_cit8","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/0003-9861(56)90251-X","article-title":"An electrophoretic\nstudy of normal and post-mortem human and bovine synovial fluids","volume":"64","author":"Platt","year":"1956","journal-title":"Arch. Biochem. Biophys."},{"key":"2026090116331622900_cit9","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1002\/art.1780241215","article-title":"Permeability\nof rheumatoid and normal human synovium to specific plasma proteins","volume":"24","author":"Levick","year":"1981","journal-title":"Arthritis Rheum."},{"key":"2026090116331622900_cit10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1477-5956-9-65","article-title":"Optimizing\nhuman synovial fluid preparation for two-dimensional gel electrophoresis","volume":"9","author":"Chen","year":"2011","journal-title":"Proteome Sci."},{"key":"2026090116331622900_cit11","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1097\/01.NAJ.0000412646.80054.21","article-title":"The impact of osteoarthritis\nin the United States:\na population-health perspective","volume":"112","author":"Murphy","year":"2012","journal-title":"Am. J. Nurs."},{"key":"2026090116331622900_cit12","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/art.23176","article-title":"Estimates\nof the prevalence of arthritis and\nother rheumatic conditions in the United States: part II","volume":"58","author":"Lawrence","year":"2008","journal-title":"Arthritis Rheum."},{"key":"2026090116331622900_cit13","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1177\/0363546512442336","article-title":"Incidence\nand risk factors for injuries to the anterior cruciate ligament in\nnational collegiate athletic association football data from the 2004\u20132005\nthrough 2008\u20132009 National Collegiate Athletic Association\nInjury Surveillance System","volume":"40","author":"Dragoo","year":"2012","journal-title":"Am. J. Sports Med."},{"key":"2026090116331622900_cit14","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1097\/01.bot.0000246468.80635.ef","article-title":"Posttraumatic\nosteoarthritis: a first estimate of incidence, prevalence, and burden\nof disease","volume":"20","author":"Brown","year":"2006","journal-title":"J. Orthop. Trauma"},{"key":"2026090116331622900_cit15","first-page":"1","article-title":"Osteoarthritis\nyear 2012 in review: biomarkers","author":"Mobasheri","year":"2012","journal-title":"Osteoarthritis\nCartilage"},{"key":"2026090116331622900_cit16","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1002\/art.37823","article-title":"Proteomic\nanalysis of synovial fluid from the osteoarthritic\nknee: comparison with transcriptome analyses of joint tissues","volume":"65","author":"Ritter","year":"2013","journal-title":"Arthritis Rheum."},{"key":"2026090116331622900_cit17","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/ar2172","article-title":"High abundance synovial\nfluid proteome: distinct profiles in health and osteoarthritis","volume":"9","author":"Gobezie","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"2026090116331622900_cit18","doi-asserted-by":"crossref","first-page":"4478","DOI":"10.1016\/j.jprot.2012.02.008","article-title":"Gambling on putative\nbiomarkers of osteoarthritis and osteochondrosis by equine synovial\nfluid proteomics","volume":"75","author":"Chiaradia","year":"2012","journal-title":"J. Proteomics"},{"key":"2026090116331622900_cit19","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.joca.2009.11.012","article-title":"Proteomics role\nin the search for improved diagnosis,\nprognosis and treatment of osteoarthritis","volume":"18","author":"Ruiz-Romero","year":"2010","journal-title":"Osteoarthritis\nCartilage"},{"key":"2026090116331622900_cit20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1559-0275-11-1","article-title":"Differential\nproteomic analysis of synovial fluid from\nrheumatoid arthritis and osteoarthritis patients","volume":"11","author":"Balakrishnan","year":"2014","journal-title":"Clin. Proteomics"},{"key":"2026090116331622900_cit21","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1128\/CDLI.8.1.105-111.2001","article-title":"Use of\ntwo-dimensional gel electrophoresis to measure changes in synovial\nfluid proteins from patients with rheumatoid arthritis treated with\nantibody to CD4","volume":"8","author":"Smith","year":"2001","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"2026090116331622900_cit22","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/1479-5876-11-210","article-title":"Innate immunity activation involved\nin unprotected porcine auto-transplant\nkidneys preserved by naked caspase-3 siRNA","volume":"11","author":"Yang","year":"2013","journal-title":"J. Transl. Med."},{"key":"2026090116331622900_cit23","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s00167-010-1382-z","article-title":"Evaluation of rotational instability\nin the anterior cruciate ligament\ndeficient knee using triaxial accelerometer: a biomechanical model\nin porcine knees","volume":"19","author":"Maeyama","year":"2011","journal-title":"Knee Surg., Sports Traumatol.,\nArthrosc."},{"key":"2026090116331622900_cit24","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/jor.21093","article-title":"A Comparison of Differential Biomarkers\nof Osteoarthritis with and\nwithout Post-traumatic Injury in the Hartley Guinea Pig Model","volume":"28","author":"Wei","year":"2010","journal-title":"J. Orthop. Res."},{"key":"2026090116331622900_cit25","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.tim.2011.11.002","article-title":"The pig: a\nmodel for human infectious diseases","volume":"20","author":"Meurens","year":"2012","journal-title":"Trends\nMicrobiol."},{"key":"2026090116331622900_cit26","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.1016\/j.jprot.2012.04.010","article-title":"Pig proteomics: a review of a species\nin the crossroad between biomedical and food sciences","volume":"75","author":"De Almeida","year":"2012","journal-title":"J. Proteomics"},{"key":"2026090116331622900_cit27","doi-asserted-by":"crossref","first-page":"R139","DOI":"10.1186\/gb-2007-8-7-r139","article-title":"A high utility integrated map of the pig genome","volume":"8","author":"Humphray","year":"2007","journal-title":"Genome Biol."},{"key":"2026090116331622900_cit28","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1177\/0363546513483446","article-title":"Use of a bioactive\nscaffold to stimulate ACL healing\nalso minimizes post-traumatic osteoarthritis after surgery","volume":"41","author":"Murray","year":"2013","journal-title":"Am. J. Sports Med."},{"key":"2026090116331622900_cit29","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.arthro.2011.10.008","article-title":"Biomechanical\noutcomes after bio-enhanced anterior cruciate ligament repair and\nanterior cruciate ligament reconstruction are equal in a porcine model","volume":"28","author":"Vavken","year":"2012","journal-title":"Arthroscopy"},{"key":"2026090116331622900_cit30","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.2106\/JBJS.I.01368","article-title":"The effect of skeletal maturity on\nfunctional healing of the anterior cruciate ligament","volume":"92","author":"Murray","year":"2010","journal-title":"J. Bone Jt. Surg. Am."},{"key":"2026090116331622900_cit31","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1074\/mcp.O112.019802","article-title":"Targeted proteomic quantification on quadrupole-orbitrap mass spectrometer","volume":"11","author":"Gallien","year":"2012","journal-title":"Mol. Cell. Proteomics"},{"key":"2026090116331622900_cit32","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1021\/ac001318c","article-title":"Detection\nof tyrosine phosphorylated peptides by precursor ion scanning quadrupole\nTOF mass spectrometry in positive ion mode","volume":"73","author":"Steen","year":"2001","journal-title":"Anal. Chem."},{"key":"2026090116331622900_cit33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1021\/ac9804902","article-title":"Mapping of phosphorylation\nsites of gel-isolated proteins by nanoelectrospray\ntandem mass spectrometry: potentials and limitations","volume":"71","author":"Neubauer","year":"1999","journal-title":"Anal. Chem."},{"key":"2026090116331622900_cit34","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1042\/bst0240893","article-title":"A strategy for identifying gel-separated proteins in sequence databases\nby MS alone","volume":"24","author":"Shevchenko","year":"1996","journal-title":"Biochem. Soc. Trans."},{"key":"2026090116331622900_cit35","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high\npeptide identification rates, individualized\np.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"Cox","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"2026090116331622900_cit36","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature10098","article-title":"Global quantification\nof mammalian gene expression control","volume":"473","author":"Schwanha\u0308usser","year":"2011","journal-title":"Nature"},{"key":"2026090116331622900_cit37","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1186\/1471-2164-9-488","article-title":"BioVenn \u2013\na web application\nfor the comparison and visualization of biological lists using area-proportional\nVenn diagrams","volume":"9","author":"Hulsen","year":"2008","journal-title":"BMC Genomics"},{"key":"2026090116331622900_cit38","unstructured":"J. C., Oliveros\n          . VENNY. An\ninteractive tool for comparing lists with Venn Diagramshttp:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/."},{"key":"2026090116331622900_cit39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1471-2199-7-3","article-title":"The RIN: an RNA integrity number for assigning integrity values to\nRNA measurements","volume":"7","author":"Schroeder","year":"2006","journal-title":"BMC Mol. Biol."},{"key":"2026090116331622900_cit40","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1002\/jbmr.1946","article-title":"An RNA-seq protocol\nto identify mRNA expression changes in mouse diaphyseal bone: applications\nin mice with bone property altering Lrp5 mutations","volume":"28","author":"Ayturk","year":"2013","journal-title":"J. Bone Miner. 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Gastroenterol."},{"key":"2026090116331622900_cit51","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1136\/ard.49.5.301","article-title":"Concentrations of\nglycosaminoglycans in synovial fluids and their relation with immunological\nand inflammatory mediators in rheumatoid arthritis","volume":"49","author":"Bensouyad","year":"1990","journal-title":"Ann. Rheum. Dis."},{"key":"2026090116331622900_cit52","first-page":"434","article-title":"Relative amounts of chondroitin sulfate\nand hyaluronic acid in synovial fluid from normal and osteochondrotic\nswine joints","volume":"48","author":"Nakano","year":"1984","journal-title":"Can. J. Comp. Med."},{"key":"2026090116331622900_cit53","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1074\/mcp.M112.024919","article-title":"Initial quantitative\nproteomic map of 28 mouse tissues using the SILAC mouse","volume":"12","author":"Geiger","year":"2013","journal-title":"Mol. Cell. Proteomics"},{"key":"2026090116331622900_cit54","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.jprot.2009.07.001","article-title":"The dynamic range problem in the analysis of the plasma\nproteome","volume":"73","author":"Hortin","year":"2010","journal-title":"J. Proteomics"},{"key":"2026090116331622900_cit55","doi-asserted-by":"crossref","first-page":"6861","DOI":"10.1073\/pnas.79.22.6861","article-title":"Isolation and characterization\nof cDNA clones for human apolipoprotein A-I","volume":"79","author":"Breslow","year":"1982","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026090116331622900_cit56","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1432-1033.1987.tb11155.x","article-title":"Iron transport and storage","volume":"164","author":"Crichton","year":"1987","journal-title":"Eur.\nJ. 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