{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:58:39Z","timestamp":1789595919711,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,15]],"date-time":"2023-01-15T00:00:00Z","timestamp":1673740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for General Medical Sciences NIH","award":["R24GM137763"],"award-info":[{"award-number":["R24GM137763"]}]},{"name":"National Institute for General Medical Sciences NIH","award":["P41GM103694"],"award-info":[{"award-number":["P41GM103694"]}]},{"name":"National Institute for General Medical Sciences NIH","award":["NOVA, AUFF-E-2016-9-27"],"award-info":[{"award-number":["NOVA, AUFF-E-2016-9-27"]}]},{"name":"National Institute for General Medical Sciences NIH","award":["R188-A6589"],"award-info":[{"award-number":["R188-A6589"]}]},{"name":"Aarhus University Research Foundation","award":["R24GM137763"],"award-info":[{"award-number":["R24GM137763"]}]},{"name":"Aarhus University Research Foundation","award":["P41GM103694"],"award-info":[{"award-number":["P41GM103694"]}]},{"name":"Aarhus University Research Foundation","award":["NOVA, AUFF-E-2016-9-27"],"award-info":[{"award-number":["NOVA, AUFF-E-2016-9-27"]}]},{"name":"Aarhus University Research Foundation","award":["R188-A6589"],"award-info":[{"award-number":["R188-A6589"]}]},{"DOI":"10.13039\/100008368","name":"Danish Rheumatoid Association","doi-asserted-by":"publisher","award":["R24GM137763"],"award-info":[{"award-number":["R24GM137763"]}],"id":[{"id":"10.13039\/100008368","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008368","name":"Danish Rheumatoid Association","doi-asserted-by":"publisher","award":["P41GM103694"],"award-info":[{"award-number":["P41GM103694"]}],"id":[{"id":"10.13039\/100008368","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008368","name":"Danish Rheumatoid Association","doi-asserted-by":"publisher","award":["NOVA, AUFF-E-2016-9-27"],"award-info":[{"award-number":["NOVA, AUFF-E-2016-9-27"]}],"id":[{"id":"10.13039\/100008368","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008368","name":"Danish Rheumatoid Association","doi-asserted-by":"publisher","award":["R188-A6589"],"award-info":[{"award-number":["R188-A6589"]}],"id":[{"id":"10.13039\/100008368","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Fibroblast-like synoviocytes (FLSs) are essential mediators in the expansive growth and invasiveness of rheumatoid synovitis, and patients with a fibroblastic-rich pauci-immune pathotype respond poorly to currently approved antirheumatic drugs. Galectin-9 (Gal-9) has been reported to directly modulate rheumatoid arthritis (RA) FLSs and to hold both pro- and anti-inflammatory properties. The objective of this study was to evaluate clinical and pathogenic aspects of Gal-9 in RA, combining national patient cohorts and cellular models. Methods: Soluble Gal-9 was measured in plasma from patients with newly diagnosed, treatment-na\u00efve RA (n = 98). The disease activity score 28-joint count C-reactive protein (DAS28CRP) and total Sharp score were used to evaluate the disease course serially over a two-year period. Plasma and synovial fluid samples were examined for soluble Gal-9 in patients with established RA (n = 18). A protein array was established to identify Gal-9 binding partners in the extracellular matrix (ECM). Synovial fluid mononuclear cells (SFMCs), harvested from RA patients, were used to obtain synovial-fluid derived FLSs (SF-FLSs) (n = 7). FLSs from patients suffering from knee Osteoarthritis (OA) were collected from patients when undergoing joint replacement surgery (n = 5). Monocultures of SF-FLSs (n = 6) and autologous co-cultures of SF-FLSs and peripheral blood mononuclear cells (PBMCs) were cultured with and without a neutralizing anti-Gal-9 antibody (n = 7). The mono- and co-cultures were subsequently analyzed by flow cytometry, MTT assay, and ELISA. Results: Patients with early and established RA had persistently increased plasma levels of Gal-9 compared with healthy controls (HC). The plasma levels of Gal-9 were associated with disease activity and remained unaffected when adding a TNF-inhibitor to their standard treatment. Gal-9 levels were elevated in the synovial fluid of established RA patients with advanced disease, compared with corresponding plasma samples. Gal-9 adhered to fibronectin, laminin and thrombospondin, while not to interstitial collagens in the ECM protein array. In vitro, a neutralizing Gal-9 antibody decreased MCP-1 and IL-6 production from both RA FLSs and OA FLSs. In co-cultures of autologous RA FLSs and PBMCs, the neutralization of Gal-9 also decreased MCP-1 and IL-6 production, without affecting the proportion of inflammatory FLSs. Conclusions: In RA, pretreatment plasma Gal-9 levels in early RA were increased and correlated with clinical disease activity. Gal-9 levels remained increased despite a significant reduction in the disease activity score in patients with early RA. The in vitro neutralization of Gal-9 decreased both MCP-1 and IL-6 production in an inflammatory subset of RA FLSs. Collectively these findings indicate that the persistent overexpression of Gal-9 in RA may modulate synovial FLS activities and could be involved in the maintenance of subclinical disease activity in RA.<\/jats:p>","DOI":"10.3390\/cells12020327","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T03:40:34Z","timestamp":1673840434000},"page":"327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Increased Galectin-9 Levels Correlate with Disease Activity in Patients with DMARD-Na\u00efve Rheumatoid Arthritis and Modulate the Secretion of MCP-1 and IL-6 from Synovial Fibroblasts"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1077-9727","authenticated-orcid":false,"given":"Morten A.","family":"Nielsen","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Rheumatology, Aarhus University Hospital, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ditte","family":"K\u00f8ster","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akul Y.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7991-2456","authenticated-orcid":false,"given":"Kristian","family":"Stengaard-Pedersen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Aarhus University Hospital, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1027-3400","authenticated-orcid":false,"given":"Pierre","family":"Busson","sequence":"additional","affiliation":[{"name":"CNRS-UMR 9018-METSY, Universit\u00e9 Paris-Saclay, Gustave Roussy, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Junker","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Odense University Hospital, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"H\u00f8rslev-Petersen","sequence":"additional","affiliation":[{"name":"Danish Hospital for Rheumatic Diseases, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merete Lund","family":"Hetland","sequence":"additional","affiliation":[{"name":"Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, 2600 Glostrup, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3690-467X","authenticated-orcid":false,"given":"Mikkel","family":"\u00d8stergaard","sequence":"additional","affiliation":[{"name":"Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, 2600 Glostrup, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malene","family":"Hvid","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4482-8945","authenticated-orcid":false,"given":"Hakon","family":"Leffler","sequence":"additional","affiliation":[{"name":"Division for Microbiology, Immunology and Glycobiology (MIG), Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tue W.","family":"Kragstrup","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Rheumatology, Aarhus University Hospital, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Cummings","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7079-1587","authenticated-orcid":false,"given":"Bent","family":"Deleuran","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Rheumatology, Aarhus University Hospital, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s41590-019-0378-1","article-title":"Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry","volume":"20","author":"Zhang","year":"2019","journal-title":"Nat Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1093\/rheumatology\/ker235","article-title":"Developing anti-TNF and biologic agents","volume":"50","author":"Taylor","year":"2011","journal-title":"Rheumatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nrrheum.2015.8","article-title":"Rheumatoid arthritis therapy reappraisal: Strategies, opportunities and challenges","volume":"11","author":"Smolen","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1002\/art.39269","article-title":"Perspectives from Masters in Rheumatology and Autoimmunity: Can We Get Closer to a Cure for Rheumatoid Arthritis?","volume":"67","author":"Feldmann","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1136\/annrheumdis-2016-210713","article-title":"Efficacy of biological disease-modifying antirheumatic drugs: A systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis","volume":"76","author":"Nam","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_6","first-page":"e000524-8","article-title":"Switching biological disease-modifying antirheumatic drugs in patients with axial spondyloarthritis: Results from a systematic literature review","volume":"3","author":"Balsa","year":"2017","journal-title":"RMD Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.berh.2014.10.024","article-title":"Molecular and cellular heterogeneity in the Rheumatoid Arthritis synovium: Clinical correlates of synovitis","volume":"28","author":"Townsend","year":"2014","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1097\/BOR.0b013e32835fd8eb","article-title":"New learnings on the pathophysiology of RA from synovial biopsies","volume":"25","author":"Pitzalis","year":"2013","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/annrheumdis-2018-214539","article-title":"Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients","volume":"78","author":"Humby","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1097\/BOR.0000000000000148","article-title":"The role of the synovial fibroblast in rheumatoid arthritis pathogenesis","volume":"27","author":"Turner","year":"2015","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13075-017-1303-3","article-title":"Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis","volume":"19","author":"Bustamante","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/s41467-018-02892-y","article-title":"Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis","volume":"9","author":"Mizoguchi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s41586-019-1263-7","article-title":"Distinct fibroblast subsets drive inflammation and damage in arthritis","volume":"570","author":"Croft","year":"2019","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41584-019-0220-z","article-title":"Single-cell technologies\u2014Studying rheumatic diseases one cell at a time","volume":"15","author":"Cheung","year":"2019","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Vilar, K.D., Pereira, M.C., Tavares Dantas, A., de Melo R\u00eago, M.J., Pitta, I.D., Pinto Duarte, \u00c2.L., and da Rocha Pitta, M.G. (2019). Galectin-9 gene (LGALS9) polymorphisms are associated with rheumatoid arthritis in Brazilian patients. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223191"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wiersma, V.R., Clarke, A., Pouwels, S.D., Perry, E., Abdullah, T.M., Kelly, C., Soyza, A.D., Hutchinson, D., Eggleton, P., and Bremer, E. (2019). Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20164046"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1002\/art.23076","article-title":"Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts","volume":"56","author":"Seki","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12887","DOI":"10.1038\/s41598-018-31173-3","article-title":"Endogenous Galectin-9 Suppresses Apoptosis in Human Rheumatoid Arthritis Synovial Fibroblasts","volume":"8","author":"Pearson","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1136\/ard.43.4.551","article-title":"Laminin and vascular proliferation in rheumatoid arthritis","volume":"43","author":"Scott","year":"1984","journal-title":"Ann. Rheum. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.1038\/s41467-018-07129-6","article-title":"Locally anchoring enzymes to tissues via extracellular glycan recognition","volume":"9","author":"Farhadi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/glycob\/3.4.297","article-title":"The family of metazoan metal-independent beta-galactoside-binding lectins: Structure, function and molecular evolution","volume":"3","author":"Hirabayashi","year":"1993","journal-title":"Glycobiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/molbev\/msh082","article-title":"Phylogenetic Analysis of the Vertebrate Galectin Family","volume":"21","author":"Houzelstein","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"ref_24","unstructured":"Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Darvill, A.G., Kinoshita, T., Packer, N.H., and Prestegard, J.H. (2017). Essentials of Glycobiology, Cold Spring Harbor Laboratory Press. [3rd ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1136\/annrheumdis-2012-202735","article-title":"Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: An investigator-initiated, randomised, double-blind, parallel-group, placebo-controlled trial","volume":"73","author":"Hetland","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1136\/annrheumdis-2015-208166","article-title":"Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction: A 2-year investigator-initiated, double-blinded, randomised, controlled trial (OPERA)","volume":"75","author":"Hetland","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.39480","article-title":"2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis","volume":"68","author":"Singh","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/S0140-6736(89)90430-3","article-title":"Inhibitory effect of TNF\u03b1 antibodies on synovial cell interleukin-1 production in rheumatoid arthritis","volume":"334","author":"Brennan","year":"1989","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1759720X19828669","DOI":"10.1177\/1759720X19828669","article-title":"IL-12\/IL-23p40 identified as a downstream target of apremilast in ex vivomodels of arthritis","volume":"11","author":"Kragstrup","year":"2019","journal-title":"Ther. Adv. Musculoskelet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/acr2.11094","article-title":"Responses to Cytokine Inhibitors Associated with Cellular Composition in Models of Immune-Mediated Inflammatory Arthritis","volume":"2","author":"Nielsen","year":"2020","journal-title":"ACR Open Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s41927-019-0093-4","article-title":"Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis","volume":"3","author":"Kragstrup","year":"2019","journal-title":"BMC Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lhuillier, C., Barjon, C., Baloche, V., Niki, T., Gelin, A., Mustapha, R., Cla\u00ebr, L., Hoos, S., Chiba, Y., and Ueno, M. (2018). Characterization of neutralizing antibodies reacting with the 213\u2013224 amino-acid segment of human galectin-9. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202512"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/2193-1801-2-263","article-title":"A simple set of validation steps identifies and removes false results in a sandwich enzyme- linked immunosorbent assay caused by anti- animal IgG antibodies in plasma from arthritis patients","volume":"2","author":"Kragstrup","year":"2013","journal-title":"SpringerPlus"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"915890","DOI":"10.3389\/fimmu.2022.915890","article-title":"Galectin-3 Decreases 4-1BBL Bioactivity by Crosslinking Soluble and Membrane Expressed 4-1BB","volume":"13","author":"Nielsen","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1093\/rheumatology\/kew237","article-title":"A disintegrin and metalloprotease-17 and galectin-9 are important regulators of local 4-1BB activity and disease outcome in rheumatoid arthritis","volume":"55","author":"Nielsen","year":"2016","journal-title":"Rheumatology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Matsumoto, H., Fujita, Y., Asano, T., Matsuoka, N., Temmoku, J., Sato, S., Yashiro\u2013Furuya, M., Yokose, K., Yoshida, S., and Suzuki, E. (2021). Association between inflammatory cytokines and immune-checkpoint molecule in rheumatoid arthritis. PLoS ONE, 16.","DOI":"10.21203\/rs.3.rs-546264\/v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41586-020-2222-z","article-title":"Notch signalling drives synovial fibroblast identity and arthritis pathology","volume":"582","author":"Wei","year":"2020","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1038\/nm.2050","article-title":"Synovial fibroblasts spread rheumatoid arthritis to unaffected joints","volume":"15","author":"Knedla","year":"2009","journal-title":"Nat Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/03009742.2021.1992860","article-title":"Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogenesis in patients with rheumatoid arthritis","volume":"52","author":"Nielsen","year":"2022","journal-title":"Scand. J. Rheumatol."},{"key":"ref_40","first-page":"7097","article-title":"The major non-integrin laminin binding protein of macrophages is identical to carbohydrate binding protein 35 (Mac-2)","volume":"265","author":"Woo","year":"1990","journal-title":"J. Biol. Chem. Am. Soc. Biochem. Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"783","DOI":"10.3389\/fmicb.2014.00783","article-title":"Interaction between extracellular matrix molecules and microbial pathogens: Evidence for the missing link in autoimmunity with rheumatoid arthritis as a disease model","volume":"5","author":"Sofat","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1002\/jcp.27026","article-title":"Role and translational implication of galectins in arthritis pathophysiology and treatment: A systematic literature review","volume":"234","author":"Salamanna","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jbspin.2016.02.029","article-title":"Galectin-3: A key player in arthritis","volume":"84","author":"Hu","year":"2017","journal-title":"Jt. Bone Spine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nri2536","article-title":"Turning \u201csweet\u201d on immunity: Galectin\u2013glycan interactions in immune tolerance and inflammation","volume":"9","author":"Rabinovich","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","first-page":"633","article-title":"Subtyping of osteoarthritic synoviopathy","volume":"20","author":"Oehler","year":"2002","journal-title":"Clin. Exp."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.semcdb.2019.12.006","article-title":"Synovial fibroblasts and articular tissue remodelling: Role and mechanisms","volume":"101","author":"Pap","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"eaba4353","DOI":"10.1126\/sciadv.aba4353","article-title":"Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal","volume":"6","author":"Svensson","year":"2020","journal-title":"Sci. Adv."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/2\/327\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:06:34Z","timestamp":1760119594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/2\/327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,15]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["cells12020327"],"URL":"https:\/\/doi.org\/10.3390\/cells12020327","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,15]]}}}