{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T14:01:28Z","timestamp":1762956088854,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T00:00:00Z","timestamp":1559088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR052873"],"award-info":[{"award-number":["AR052873"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shared Instrumentation Grant","award":["S10 OD010584-01A1","S10 OD018338-01"],"award-info":[{"award-number":["S10 OD010584-01A1","S10 OD018338-01"]}]},{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","award":["17-A0-00-000269"],"award-info":[{"award-number":["17-A0-00-000269"]}],"id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: To investigate the expression of vascular adhesion protein-1 (VAP-1) in joint tissues and serum in symptomatic knee osteoarthritis (SKOA) patients and examine whether VAP-1 levels predict increased risk of disease severity in a cross-sectional study. Methods: Baseline VAP-1 expression and soluble VAP-1 (sVAP-1) levels were assessed in the synovium synovial fluid and in the serum in cohorts of patients with tibiofemoral medial knee OA and healthy subjects. Standardized fixed-flexion poster anterior knee radiographs scored for Kellgren\u2013Lawrence (KL) grade (0\u20134) and medial joint space width (JSW). KL1\/2 vs. KL3\/4 scores defined early and advanced radiographic severity, respectively. Biochemical markers assessed in serum or synovial fluids (SF) comprised sVAP-1, interleukin 1 receptor antagonist (IL-1Ra), interleukin 6 (IL-6), soluble receptor for advanced glycation end-products (sRAGE), C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 4 (CCL4), cluster of differentiation 163 (CD163), high sensitivity C-reactive protein (hsCRP), and matrix metalloproteinases (MMPs)-1,-3,-9. Associations between biomarkers and radiographic severity KL1\/2 vs. KL3\/4 (logistic regression controlling for covariates) and pain (Spearman correlation) were evaluated. Results: Elevated levels of sVAP-1 observed in OA synovial fluid and VAP-1 expression in synovium based on immunohistochemical, microarray, and real-time quantitative polymerase chain reaction (qRT-PCR) analyses. However, serum sVAP-1 levels in OA patients were lower than in controls and inversely correlated with pain and inflammation markers (hsCRP and soluble RAGE). Soluble VAP-1 levels in serum were also lower in radiographically advanced (KL3\/4) compared with early KL1\/2 knee SKOA patients. Conclusion: Local (synovial fluid) semicarbazide-sensitive amine oxidase (SSAO)\/sVAP-1 levels were elevated in OA and correlated with radiographic severity. However, systemic (serum) sVAP-1 levels were lower in SKOA patients than normal and inversely correlated with pain and inflammation markers. Serum sVAP-1 levels were higher in early (KL1\/2) compared with advanced (KL3\/4) SKOA patients.<\/jats:p>","DOI":"10.3390\/ijms20112642","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T11:31:28Z","timestamp":1559129488000},"page":"2642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Vascular Adhesion Protein-1 (VAP-1) as Predictor of Radiographic Severity in Symptomatic Knee Osteoarthritis in the New York University Cohort"],"prefix":"10.3390","volume":"20","author":[{"given":"Eirini","family":"Bournazou","sequence":"first","affiliation":[{"name":"Roche Innovation Center New York, New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Samuels","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY 10003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Krasnokutsky","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY 10003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyoti","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY 10003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianzhen","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY 10003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Bencardino","sequence":"additional","affiliation":[{"name":"Department of Radiology, NYU Langone Medical Center\/NYU School of Medicine, New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon","family":"Rybak","sequence":"additional","affiliation":[{"name":"Department of Radiology, NYU Langone Medical Center\/NYU School of Medicine, New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven B.","family":"Abramson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY 10003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Junker","sequence":"additional","affiliation":[{"name":"Roche Innovation Center Basel, CH-4070 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen S.","family":"Brown","sequence":"additional","affiliation":[{"name":"Roche Innovation Center New York, New York, NY 10016, USA"},{"name":"Roche Innovation Center Basel, CH-4070 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7080-8118","authenticated-orcid":false,"given":"Mukundan","family":"Attur","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY 10003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/BOR.0000000000000479","article-title":"Epidemiology of osteoarthritis: literature update","volume":"30","author":"Vina","year":"2018","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/ncprheum0193","article-title":"Prospects for disease modification in osteoarthritis","volume":"2","author":"Abramson","year":"2006","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.joca.2012.11.012","article-title":"Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)","volume":"21","author":"Berenbaum","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.joca.2013.12.004","article-title":"TSG-6 activity as a novel biomarker of progression in knee osteoarthritis","volume":"22","author":"Wisniewski","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1002\/1529-0131(200106)44:6<1237::AID-ART214>3.0.CO;2-F","article-title":"Osteoarthritis, an inflammatory disease: Potential implication for the selection of new therapeutic targets","volume":"44","author":"Pelletier","year":"2001","journal-title":"Arthritis Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"R7","DOI":"10.1186\/ar3555","article-title":"Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4","volume":"14","author":"Sohn","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1002\/art.30360","article-title":"Increased interleukin-1\u03b2 gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis","volume":"63","author":"Attur","year":"2011","journal-title":"Arthritis Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/j.joca.2015.08.006","article-title":"Plasma levels of interleukin-1 receptor antagonist (IL1Ra) predict radiographic progression of symptomatic knee osteoarthritis","volume":"23","author":"Attur","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1126\/science.1529341","article-title":"A 90-kilodalton endothelial cell molecule mediating lymphocyte binding in humans","volume":"257","author":"Salmi","year":"1992","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1084\/jem.188.1.17","article-title":"Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion molecule","volume":"188","author":"Smith","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4228","DOI":"10.4049\/jimmunol.151.8.4228","article-title":"Lymphocyte-vascular adhesion protein-2 is a novel 70-kDa molecule involved in lymphocyte adhesion to vascular endothelium","volume":"151","author":"Airas","year":"1993","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1084\/jem.178.6.2255","article-title":"Induction and function of vascular adhesion protein-1 at sites of inflammation","volume":"178","author":"Salmi","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0002-9440(10)64558-0","article-title":"In vivo detection of vascular adhesion protein-1 in experimental inflammation","volume":"157","author":"Jaakkola","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6160","DOI":"10.4049\/jimmunol.179.9.6160","article-title":"VAP-1-deficient mice display defects in mucosal immunity and antimicrobial responses: Implications for antiadhesive applications","volume":"179","author":"Koskinen","year":"2007","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s00281-014-0417-9","article-title":"Ectoenzymes in leukocyte migration and their therapeutic potential","volume":"36","author":"Salmi","year":"2014","journal-title":"Semin. Immunopathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1002\/art.22061","article-title":"Vascular amine oxidases are needed for leukocyte extravasation into inflamed joints in vivo","volume":"54","author":"Smith","year":"2006","journal-title":"Arthritis Rheumatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.phrs.2018.02.006","article-title":"Analgesic effects of the novel semicarbazide-sensitive amine oxidase inhibitor SZV 1287 in mouse pain models with neuropathic mechanisms: Involvement of transient receptor potential vanilloid 1 and ankyrin 1 receptors","volume":"131","author":"Bencze","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1128\/IAI.69.3.1774-1780.2001","article-title":"Expression of adhesion molecules in synovia of patients with treatment-resistant lyme arthritis","volume":"69","author":"Akin","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.joca.2016.01.340","article-title":"Expression of the semicarbazide-sensitive amine oxidase in articular cartilage: Its role in terminal differentiation of chondrocytes in rat and human","volume":"24","author":"Filip","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.joca.2008.05.004","article-title":"Serum protein signatures detect early radiographic osteoarthritis","volume":"17","author":"Ling","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_21","first-page":"1833","article-title":"Validation study of WOMAC: A health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee","volume":"15","author":"Bellamy","year":"1988","journal-title":"J. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.joca.2005.04.014","article-title":"A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis","volume":"13","author":"Srikanth","year":"2005","journal-title":"Osteoarthr. Cartil."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.berh.2009.08.006","article-title":"Why is osteoarthritis an age-related disease?","volume":"24","author":"Loeser","year":"2010","journal-title":"Best Pract Res. Clin. Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bedson, J., and Croft, P.R. (2008). The discordance between clinical and radiographic knee osteoarthritis: a systematic search and summary of the literature. BMC Musculoskelet. Disord., 9.","DOI":"10.1186\/1471-2474-9-116"},{"key":"ref_25","first-page":"1513","article-title":"Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee","volume":"27","author":"Hannan","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"iv34","DOI":"10.1093\/rheumatology\/kex417","article-title":"Is osteoarthritis one disease or a collection of many?","volume":"57","author":"Deveza","year":"2018","journal-title":"Rheumatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrrheum.2014.162","article-title":"Emerging regulators of the inflammatory process in osteoarthritis","volume":"11","author":"Terkeltaub","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nrrheum.2016.136","article-title":"Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis","volume":"12","author":"Robinson","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/BOR.0b013e32835a9381","article-title":"Prognostic biomarkers in osteoarthritis","volume":"25","author":"Attur","year":"2013","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1002\/art.39279","article-title":"Low-grade inflammation in symptomatic knee osteoarthritis: Prognostic value of inflammatory plasma lipids and peripheral blood leukocyte biomarkers","volume":"67","author":"Attur","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41366-018-0172-4","article-title":"Serum vascular adhesion protein-1 is up-regulated in hyperglycemia and is associated with incident diabetes negatively","volume":"43","author":"Kuo","year":"2019","journal-title":"Int. J. Obes."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1096\/fj.15-272427","article-title":"Elevated expression of periostin in human osteoarthritic cartilage and its potential role in matrix degradation via matrix metalloproteinase-13","volume":"29","author":"Attur","year":"2015","journal-title":"FASEB J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1002\/art.34399","article-title":"Orphan nuclear receptor NR4A2 induces synoviocyte proliferation, invasion, and matrix metalloproteinase 13 transcription","volume":"64","author":"Mix","year":"2012","journal-title":"Arthritis Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u2206\u2206Ct Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/11\/2642\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:54:22Z","timestamp":1760187262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/11\/2642"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,29]]},"references-count":34,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["ijms20112642"],"URL":"https:\/\/doi.org\/10.3390\/ijms20112642","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2019,5,29]]}}}