{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:20:37Z","timestamp":1791328837528,"version":"4.3.1"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["642414"],"award-info":[{"award-number":["642414"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006315","name":"ReumaNederland","doi-asserted-by":"publisher","award":["LLP12"],"award-info":[{"award-number":["LLP12"]}],"id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pro-inflammatory cytokines are considered to play a major role in osteoarthritis (OA), yet so far, the specific cytokines involved in the pathology of OA have not been identified. Oncostatin M (OSM) is a cytokine from the interleukin 6 (IL-6) family that has been shown to be elevated in synovial fluid of most rheumatoid arthritis (RA) patients, but only in a limited subset of OA patients. Little is known about OSM in the different joint tissues during OA and how its expression correlates with hallmarks of disease. Here, we mapped OSM expression in the joint tissues of two rat models of arthritis: an acute inflammatory model and an instability-induced osteoarthritic model. OSM expression was correlated with hallmarks of OA, namely cartilage damage, synovitis, and osteophyte formation. Reanalysis of an existing dataset on cytokine profiling of OA synovial fluid was performed to assess pattern differences between patients positive and negative for OSM. In the inflammatory model, OSM expression correlated with synovitis and osteophyte formation but not with cartilage damage. On the contrary, in the instability model of OA, an increase in synovitis, cartilage damage, and osteophyte formation was observed without changes in OSM expression. In line with these findings, synovial fluid of OA patients with detectable OSM contained higher levels of other inflammatory cytokines, namely interferon gamma (IFN-\u03b3), IL-1\u03b1 and tumor necrosis factor alpha (TNF-\u03b1), likely indicating a more inflammatory state. Taken together these data indicate OSM might play a prominent role in inflammatory phenotypes of OA.<\/jats:p>","DOI":"10.3390\/cells10030508","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T20:55:44Z","timestamp":1614459344000},"page":"508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Association between Oncostatin M Expression and Inflammatory Phenotype in Experimental Arthritis Models and Osteoarthritis Patients"],"prefix":"10.3390","volume":"10","author":[{"given":"Joao Pedro","family":"Garcia","sequence":"first","affiliation":[{"name":"Department of Orthopedics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2214-2344","authenticated-orcid":false,"given":"Lizette","family":"Utomo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery &amp; Special Dental Care, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imke","family":"Rudnik-Jansen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3400-9559","authenticated-orcid":false,"given":"Jie","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas P.A.","family":"Zuithoff","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Krouwels","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1852-6409","authenticated-orcid":false,"given":"Gerjo J.V.M.","family":"van Osch","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Otorhinolaryngology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1585-3052","authenticated-orcid":false,"given":"Laura B.","family":"Creemers","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"ref_1","first-page":"646","article-title":"Burden of major musculoskeletal conditions","volume":"81","author":"Woolf","year":"2003","journal-title":"Bull. World Health Organ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/jcp.21258","article-title":"Osteoarthritis","volume":"213","author":"Goldring","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/BOR.0b013e328349c2b1","article-title":"Inflammation in osteoarthritis","volume":"23","author":"Goldring","year":"2011","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/S0140-6736(11)60243-2","article-title":"Osteoarthritis: An update with relevance for clinical practice","volume":"377","author":"Bijlsma","year":"2011","journal-title":"Lancet"},{"key":"ref_5","unstructured":"Schue, J.R., Tawfik, O., Smith, D.D., Hinson, G., Bolce, R., Wick, J.A., and Lindsley, H.B. (2011, January 4). Treatment of knee osteoarthritis with intraarticular infliximab may improve knee function and reduce synovial infiltration by macrophages. Proceedings of the Annual Scientific Meeting of the American College of Rheumatology and Association of Rheumatology Health Professionals, Chicago, IL, USA."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/art.24096","article-title":"Intraarticular injection of anakinra in osteoarthritis of the knee: A multicenter, randomized, double-blind, placebo-controlled study","volume":"61","author":"Chevalier","year":"2009","journal-title":"Arthritis Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/art.40840","article-title":"A phase II trial of lutikizumab, an anti\u2013interleukin-1\u03b1\/\u03b2 dual variable domain immunoglobulin, in knee osteoarthritis patients with synovitis","volume":"71","author":"Fleischmann","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_8","first-page":"1650","article-title":"A high interleukin 1 receptor antagonist\/IL-1beta ratio occurs naturally in knee osteoarthritis","volume":"35","author":"Richette","year":"2008","journal-title":"J. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1007\/s00296-014-3016-0","article-title":"Soluble TNF receptors are produced at sites of inflammation and are inversely associated with self-reported symptoms (WOMAC) in knee osteoarthritis","volume":"34","author":"Almeida","year":"2014","journal-title":"Rheumatol. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1136\/ard.56.3.184","article-title":"Detection of oncostatin M in synovial fluid from patients with rheumatoid arthritis","volume":"56","author":"Hui","year":"1997","journal-title":"Ann. Rheum. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1002\/1529-0131(199810)41:10<1760::AID-ART8>3.0.CO;2-M","article-title":"The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint","volume":"41","author":"Cawston","year":"1998","journal-title":"Arthritis Rheum."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3152","DOI":"10.1002\/art.22161","article-title":"Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures","volume":"54","author":"Fearon","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"R57","DOI":"10.1186\/ar1460","article-title":"A model of inflammatory arthritis highlights a role for oncostatin M in pro-inflammatory cytokine-induced bone destruction via RANK\/RANKL","volume":"7","author":"Hui","year":"2005","journal-title":"Arthritis Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.joca.2007.05.002","article-title":"Mechanism of proteoglycan aggregate degradation in cartilage stimulated with oncostatin M","volume":"16","author":"Durigova","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/512103","article-title":"The enigmatic cytokine oncostatin M and roles in disease","volume":"2013","author":"Richards","year":"2013","journal-title":"ISRN Inflamm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1016\/S0002-9440(10)64330-1","article-title":"Adenoviral gene transfer of interleukin-1 in combination with oncostatin M induces significant joint damage in a murine model","volume":"162","author":"Rowan","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.1002\/art.11333","article-title":"Oncostatin M in combination with tumor necrosis factor? induces cartilage damage and matrix metalloproteinase expression in vitro and in vivo","volume":"48","author":"Hui","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/1529-0131(200002)43:2<281::AID-ANR7>3.0.CO;2-7","article-title":"Synovial fluid levels of tumor necrosis factor \u03b1 and oncostatin M correlate with levels of markers of the degradation of crosslinked collagen and cartilage aggrecan in rheumatoid arthritis but not in osteoarthritis","volume":"43","author":"Manicourt","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"80","DOI":"10.22203\/eCM.v026a06","article-title":"Inhibition of oncostatin M in osteoarthritic synovial fluid enhances GAG production in osteoarthritic cartilage repair","volume":"26","author":"Beekhuizen","year":"2013","journal-title":"Eur. Cells Mater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1186\/s13075-014-0441-0","article-title":"Cytokine profiles in the joint depend on pathology, but are different between synovial fluid, cartilage tissue and cultured chondrocytes","volume":"16","author":"Tsuchida","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1006\/cyto.2000.0747","article-title":"gp130 Cytokine family and bone cells","volume":"12","author":"Heymann","year":"2000","journal-title":"Cytokine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/S0002-9440(10)61120-0","article-title":"Adenoviral transfer of murine oncostatin M elicits periosteal bone apposition in knee joints of mice, despite synovial inflammation and up-regulated expression of interleukin-6 and receptor activator of nuclear factor-kappa B ligand","volume":"160","author":"Bennink","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1172\/JCI40568","article-title":"Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice","volume":"120","author":"Walker","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1002\/art.20166","article-title":"Secretion of oncostatin M by neutrophils in rheumatoid arthritis","volume":"50","author":"Cross","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.4049\/jimmunol.139.9.2977","article-title":"Purification and characterization of cytostatic lymphokines produced by activated human T lymphocytes. Synergistic antiproliferative activity of transforming growth factor beta 1, interferon-gamma, and oncostatin M for human melanoma cells","volume":"139","author":"Brown","year":"1987","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jaci.2007.08.054","article-title":"Human mast cells release oncostatin M on contact with activated T cells: Possible biologic relevance","volume":"121","author":"Salamon","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.joca.2012.08.027","article-title":"Synovial inflammation, immune cells and their cytokines in osteoarthritis: A review","volume":"20","author":"Zuurmond","year":"2012","journal-title":"Osteoarthr. Cartil."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1084\/jem.146.6.1585","article-title":"Arthritis in rats after systemic injection of streptococcal cells or cell walls","volume":"146","author":"Cromartie","year":"1977","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00590-013-1205-2","article-title":"Useful animal models for the research of osteoarthritis","volume":"24","author":"Lelovas","year":"2014","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1080\/10717544.2019.1568625","article-title":"Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model","volume":"26","author":"Schrijver","year":"2019","journal-title":"Drug Deliv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4050","DOI":"10.1111\/bph.14817","article-title":"Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing","volume":"176","author":"Tellegen","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"424","DOI":"10.2106\/00004623-197052030-00002","article-title":"Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips","volume":"52","author":"Mankin","year":"1970","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1365-2559.2006.02508.x","article-title":"Synovitis score: Discrimination between chronic low-grade and high-grade synovitis","volume":"49","author":"Krenn","year":"2006","journal-title":"Histopathology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jcm.2016.02.012","article-title":"A guideline of selecting and reporting intraclass correlation coefficients for reliability research","volume":"15","author":"Koo","year":"2016","journal-title":"J. Chiropr. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1002\/jbmr.193","article-title":"Gene expression patterns in bone following mechanical loading","volume":"26","author":"Roosa","year":"2011","journal-title":"J. Bone Min. Res."},{"key":"ref_36","unstructured":"Pasta, D.J., and Miriam, G. (2003, January 30). Cisternas: Estimating standard errors for class variables in generalized linear models using PROC IML. Proceedings of the SAS Conference Proceedings: SAS Users Group International 28, Seattle, WA, USA."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nrrheum.2014.80","article-title":"The multifactorial role of neutrophils in rheumatoid arthritis","volume":"10","author":"Wright","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1007\/s10067-016-3170-8","article-title":"Is blood neutrophil-lymphocyte ratio an independent predictor of knee osteoarthritis severity?","volume":"35","author":"Onat","year":"2016","journal-title":"Clin. Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"21703","DOI":"10.1074\/jbc.M116.748483","article-title":"Murine oncostatin M acts via leukemia inhibitory factor receptor to phosphorylate signal transducer and activator of transcription 3 (STAT3) but not STAT1, an effect that protects bone mass","volume":"291","author":"Walker","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/ar1518","article-title":"The effects of inflammatory arthritis on bone remodeling","volume":"7","author":"Goldring","year":"2005","journal-title":"Arthritis Res. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"R32","DOI":"10.1186\/ar4461","article-title":"Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage","volume":"16","author":"Siebelt","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/jbm4.10029","article-title":"Early signs of bone and cartilage changes induced by treadmill exercise in rats","volume":"2","author":"Moshtagh","year":"2018","journal-title":"JBMR Plus"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/art.11422","article-title":"Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation","volume":"50","author":"Blom","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.joca.2004.03.003","article-title":"Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis","volume":"12","author":"Blom","year":"2004","journal-title":"Osteoarthr. Cartil."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rudnik-Jansen, I., Woike, N., De Jong, S., Versteeg, S., Kik, M., Emans, P., Mihov, G., Thies, J., Eijkelkamp, N., and Tryfonidou, M. (2019). Applicability of a modified rat model of acute arthritis for long-term testing of drug delivery systems. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11020070"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.joca.2016.10.011","article-title":"Controlling joint instability delays the degeneration of articular cartilage in a rat model","volume":"25","author":"Murata","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/jor.22208","article-title":"Acute and late changes in intraarticular cytokine levels following anterior cruciate ligament injury","volume":"31","author":"Bigoni","year":"2012","journal-title":"J. Orthop. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.arthro.2005.08.034","article-title":"Inflammatory cytokine profiles associated with chondral damage in the anterior cruciate ligament\u2013deficient knee","volume":"21","author":"Marks","year":"2005","journal-title":"Arthrosc. J. Arthrosc. Relat. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.joca.2011.12.009","article-title":"Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: A randomized controlled pilot trial (NCT00332254)","volume":"20","author":"Kraus","year":"2012","journal-title":"Osteoarthr. Cartil."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/3\/508\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:30:01Z","timestamp":1760160601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/3\/508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,27]]},"references-count":49,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["cells10030508"],"URL":"https:\/\/doi.org\/10.3390\/cells10030508","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,27]]}}}