{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:29:33Z","timestamp":1773804573628,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T00:00:00Z","timestamp":1572480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)","award":["NORTE-01-0145-FEDER-000012"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000012"]}]},{"DOI":"10.13039\/501100001702","name":"AO Foundation","doi-asserted-by":"publisher","award":["S-15-83S"],"award-info":[{"award-number":["S-15-83S"]}],"id":[{"id":"10.13039\/501100001702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/112832\/2015, SFRH\/BD\/85968\/2012, PD\/BD\/135489\/2018, DL 57\/2016\/CP1360\/CT0008 and DL 57\/2016\/CP1360\/CT0004"],"award-info":[{"award-number":["SFRH\/BD\/112832\/2015, SFRH\/BD\/85968\/2012, PD\/BD\/135489\/2018, DL 57\/2016\/CP1360\/CT0008 and DL 57\/2016\/CP1360\/CT0004"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a systemic disease that affects the osteoarticular system, associated with bone fragility and increased risk of fractures. Herein, we aimed to characterize the systemic impact of the rat collagen-induced arthritis (CIA) model and explore its combination with femoral bone defect (FD). The impact of CIA on endogenous mesenchymal stem\/stromal cells (MSC) was also investigated. CIA induction led to enlarged, more proliferative, spleen and draining lymph nodes, with altered proportion of lymphoid populations. Upon FD, CIA animals increased the systemic myeloid cell proportions, and their expression of co-stimulatory molecules CD40 and CD86. Screening plasma cytokine\/chemokine levels showed increased tumor necrosis factor-\u03b1 (TNF-\u03b1), Interleukin (IL)-17, IL-4, IL-5, and IL-12 in CIA, and IL-2 and IL-6 increased in CIA and CIA+FD, while Fractalkine and Leptin were decreased in both groups. CIA-derived MSC showed lower metabolic activity and proliferation, and significantly increased osteogenic and chondrogenic differentiation markers. Exposure of control-MSC to TNF-\u03b1 partially mimicked the CIA-MSC phenotype in vitro. In conclusion, inflammatory conditions of CIA led to alterations in systemic immune cell proportions, circulating mediators, and in endogenous MSC. CIA animals respond to FD, and the combined model can be used to study the mechanisms of bone repair in inflammatory conditions.<\/jats:p>","DOI":"10.3390\/ijms20215436","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T12:38:23Z","timestamp":1572525503000},"page":"5436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5205-9069","authenticated-orcid":false,"given":"Jos\u00e9 H.","family":"Teixeira","sequence":"first","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade and INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Molecular Biology, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Andreia M.","family":"Silva","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade and INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Molecular Biology, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-8587","authenticated-orcid":false,"given":"Maria In\u00eas","family":"Almeida","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade and INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0364-5168","authenticated-orcid":false,"given":"Mafalda","family":"Bessa-Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade and INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Molecular Biology, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9096-5644","authenticated-orcid":false,"given":"Carla","family":"Cunha","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade and INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"M\u00e1rio A.","family":"Barbosa","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade and INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Molecular Biology, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-2978","authenticated-orcid":false,"given":"Susana G.","family":"Santos","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade and INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Molecular Biology, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.berh.2018.10.005","article-title":"Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis","volume":"32","year":"2018","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_2","first-page":"286","article-title":"Extra-articular manifestations in rheumatoid arthritis","volume":"5","author":"Cojocaru","year":"2010","journal-title":"Maedica (Buchar)"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s12016-016-8547-6","article-title":"The impact of conventional and biological disease modifying antirheumatic drugs on bone biology. Rheumatoid arthritis as a case study","volume":"51","author":"Barreira","year":"2016","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1007\/s00198-017-4170-5","article-title":"Skeletal complications of rheumatoid arthritis","volume":"28","author":"Heinlen","year":"2017","journal-title":"Osteoporos. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1007\/s00198-018-4473-1","article-title":"Incidence of fractures among patients with rheumatoid arthritis: A systematic review and meta-analysis","volume":"29","author":"Jin","year":"2018","journal-title":"Osteoporos. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00198-011-1584-3","article-title":"Prevalence of vertebral fractures in patients with rheumatoid arthritis: Revisiting the role of glucocorticoids","volume":"23","author":"Ghazi","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrrheum.2012.1","article-title":"Fracture healing under healthy and inflammatory conditions","volume":"8","author":"Claes","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.pathophys.2005.07.011","article-title":"Animal models of rheumatoid arthritis and their relevance to human disease","volume":"12","author":"Kannan","year":"2005","journal-title":"Pathophysiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1084\/jem.146.3.857","article-title":"Autoimmunity to type ii collagen an experimental model of arthritis","volume":"146","author":"Trentham","year":"1977","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1002\/art.27503","article-title":"Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?","volume":"62","author":"Bevaart","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_11","first-page":"377","article-title":"Animal models of rheumatoid arthritis","volume":"1","author":"Bendele","year":"2001","journal-title":"J. Musculoskelet Neuronal Interact"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1046\/j.1365-2249.1997.3181214.x","article-title":"Cytokine production in synovial tissue of mice with collagen-induced arthritis (cia)","volume":"107","author":"Mussener","year":"1997","journal-title":"Clin. Exp. Immunol."},{"key":"ref_13","first-page":"507","article-title":"Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (cia)","volume":"107","author":"Williams","year":"1997","journal-title":"Clin. Exp. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.3389\/fimmu.2018.03102","article-title":"Plumbagin ameliorates collagen-induced arthritis by regulating treg\/th17 cell imbalances and suppressing osteoclastogenesis","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_15","first-page":"15.5.1","article-title":"Collagen-induced arthritis","volume":"20","author":"Rosloniec","year":"2001","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.intimp.2013.04.012","article-title":"Torilin ameliorates type ii collagen-induced arthritis in mouse model of rheumatoid arthritis","volume":"16","author":"Endale","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1046\/j.1365-2567.2001.01267.x","article-title":"The genetic and immunopathological processes underlying collagen-induced arthritis","volume":"103","author":"Luross","year":"2001","journal-title":"Immunology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1136\/annrheumdis-2015-208918","article-title":"Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (cx611): Results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase ib\/iia clinical trial","volume":"76","author":"Jover","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/sctm.18-0031","article-title":"Intravenous infusion of umbilical cord blood-derived mesenchymal stem cells in rheumatoid arthritis: A phase ia clinical trial","volume":"7","author":"Park","year":"2018","journal-title":"Stem Cells Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2062","DOI":"10.1038\/cddis.2015.327","article-title":"Mesenchymal stem cells and immunomodulation: Current status and future prospects","volume":"7","author":"Gao","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1097\/BOR.0000000000000370","article-title":"Mesenchymal stem cells for the management of rheumatoid arthritis: Immune modulation, repair or both?","volume":"29","author":"Ansboro","year":"2017","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1002\/art.37894","article-title":"Adoptive transfer of human gingiva-derived mesenchymal stem cells ameliorates collagen-induced arthritis via suppression of th1 and th17 cells and enhancement of regulatory t cell differentiation","volume":"65","author":"Chen","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"28915","DOI":"10.1038\/srep28915","article-title":"Mesenchymal stem cells alleviate experimental rheumatoid arthritis through microrna-regulated ikappab expression","volume":"6","author":"Yan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1002\/art.22511","article-title":"Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis","volume":"56","author":"Augello","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12777","DOI":"10.1038\/srep12777","article-title":"Allogeneic mesenchymal stem cells inhibited t follicular helper cell generation in rheumatoid arthritis","volume":"5","author":"Liu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0002-9440(10)63991-0","article-title":"Dynamics of early synovial cytokine expression in rodent collagen-induced arthritis: A therapeutic study using a macrophage-deactivating compound","volume":"158","author":"Palmblad","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fimmu.2012.00077","article-title":"Inflammation and bone destruction in arthritis: Synergistic activity of immune and mesenchymal cells in joints","volume":"3","author":"Komatsu","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1002\/eji.200939578","article-title":"Animal models of rheumatoid arthritis","volume":"39","author":"Asquith","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1172\/JCI109136","article-title":"Passive transfer by cells of type ii collagen-induced arthritis in rats","volume":"62","author":"Trentham","year":"1978","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7209","DOI":"10.1016\/j.actbio.2013.04.008","article-title":"Adsorbed fibrinogen leads to improved bone regeneration and correlates with differences in the systemic immune response","volume":"9","author":"Santos","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jobaz.2012.12.005","article-title":"Lymph node histopathological studies in a combined adjuvant\u2013collagen induced arthritis model in albino rat rattus rattus","volume":"66","author":"Ibraheem","year":"2013","journal-title":"J. Basic Appl. Zool."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10787-015-0241-4","article-title":"Applying refinement to the use of mice and rats in rheumatoid arthritis research","volume":"23","author":"Hawkins","year":"2015","journal-title":"Inflammopharmacology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1002\/jor.24060","article-title":"Fracture healing in a collagen-induced arthritis rat model: Radiology and histology evidence","volume":"36","author":"Hu","year":"2018","journal-title":"J. Orthop. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/cei.12313","article-title":"Collagen-induced arthritis: Severity and immune response attenuation using multivalent n-acetyl glucosamine","volume":"177","author":"Richter","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/cei.13098","article-title":"Driving chronicity in rheumatoid arthritis: Perpetuating role of myeloid cells","volume":"193","author":"Alivernini","year":"2018","journal-title":"Clin. Exp. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6378","DOI":"10.4049\/jimmunol.0903951","article-title":"Identifying the cells breaching self-tolerance in autoimmunity","volume":"184","author":"Benson","year":"2010","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1002\/art.10410","article-title":"A subset of natural killer cells is greatly expanded within inflamed joints","volume":"46","author":"Dalbeth","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1365-2567.2007.02638.x","article-title":"Activating and inhibitory receptors on synovial fluid natural killer cells of arthritis patients: Role of cd94\/nkg2a in control of cytokine secretion","volume":"122","author":"Berg","year":"2007","journal-title":"Immunology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1002\/art.23760","article-title":"Natural killer cell degeneration exacerbates experimental arthritis in mice via enhanced interleukin-17 production","volume":"58","author":"Lo","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.biomaterials.2016.10.004","article-title":"Fibrinogen scaffolds with immunomodulatory properties promote in vivo bone regeneration","volume":"111","author":"Vasconcelos","year":"2016","journal-title":"Biomaterials"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.7150\/thno.24444","article-title":"Profiling the circulating mirnome reveals a temporal regulation of the bone injury response","volume":"8","author":"Silva","year":"2018","journal-title":"Theranostics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"v3","DOI":"10.1093\/rheumatology\/kes113","article-title":"Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis","volume":"51","author":"Choy","year":"2012","journal-title":"Rheumatology (Oxford)"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1002\/1529-0131(200006)43:6<1266::AID-ANR9>3.0.CO;2-P","article-title":"Temporal expression of inflammatory cytokines and chemokines in rat adjuvant-induced arthritis","volume":"43","author":"Szekanecz","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1023\/A:1027351111240","article-title":"Cytokine and nitric oxide production in the acute phase of bacterial cell wall-induced arthritis","volume":"21","author":"Fuseler","year":"1997","journal-title":"Inflammation"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Timmen, M., Hidding, H., Wieskotter, B., Baum, W., Pap, T., Raschke, M.J., Schett, G., Zwerina, J., and Stange, R. (2014). Influence of antitnf-alpha antibody treatment on fracture healing under chronic inflammation. BMC Musculoskelet Disord, 15.","DOI":"10.1186\/1471-2474-15-184"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2741\/s53","article-title":"Chemokines and chemokine receptors in arthritis","volume":"2","author":"Szekanecz","year":"2010","journal-title":"Front. Biosci (Schol Ed.)"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/art.1780360605","article-title":"Expression of monocyte chemotactic and activating factor in rheumatoid arthritis. Regulation of its production in synovial cells by interleukin-1 and tumor necrosis factor","volume":"36","author":"Akahoshi","year":"1993","journal-title":"Arthritis Rheum."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/ar86","article-title":"Macrophages in rheumatoid arthritis","volume":"2","author":"Kinne","year":"2000","journal-title":"Arthritis Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"R158","DOI":"10.1186\/ar2838","article-title":"Regulation of pathogenic il-17 responses in collagen-induced arthritis: Roles of endogenous interferon-gamma and il-4","volume":"11","author":"Sarkar","year":"2009","journal-title":"Arthritis Res. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.bbi.2018.11.311","article-title":"Sexual dimorphism in th17\/treg axis in lymph nodes draining inflamed joints in rats with collagen-induced arthritis","volume":"76","author":"Dimitrijevic","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.4049\/jimmunol.165.3.1557","article-title":"Heterogeneous effects of il-2 on collagen-induced arthritis","volume":"165","author":"Thornton","year":"2000","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.4049\/jimmunol.1701502","article-title":"Il-2-anti-il-2 monoclonal antibody immune complexes inhibit collagen-induced arthritis by augmenting regulatory t cell functions","volume":"201","author":"Yokoyama","year":"2018","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1093\/intimm\/dxp102","article-title":"Il-5- and eosinophil-mediated inflammation: From discovery to therapy","volume":"21","author":"Kouro","year":"2009","journal-title":"Int. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"26021","DOI":"10.1038\/srep26021","article-title":"Analysis of serum immune markers in seropositive and seronegative rheumatoid arthritis and in high-risk seropositive arthralgia patients","volume":"6","author":"Chalan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/eji.1830250123","article-title":"T helper subset involvement in two high antibody responder lines of mice (biozzi mice): Hi (susceptible) and hii (resistant) to collagen-induced arthritis","volume":"25","author":"Mevel","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/art.40688","article-title":"Role of anti-fractalkine antibody in suppression of joint destruction by inhibiting migration of osteoclast precursors to the synovium in experimental arthritis","volume":"71","author":"Ohkuro","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7010","DOI":"10.4049\/jimmunol.173.11.7010","article-title":"Inhibition of fractalkine ameliorates murine collagen-induced arthritis","volume":"173","author":"Nanki","year":"2004","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1002\/art.34637","article-title":"Leptin exacerbates collagen-induced arthritis via enhancement of th17 cell response","volume":"64","author":"Deng","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1007\/s00776-015-0768-7","article-title":"Hyperleptinemia suppresses aggravation of arthritis of collagen-antibody-induced arthritis in mice","volume":"20","author":"Okano","year":"2015","journal-title":"J. Orthop. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/cei.12372","article-title":"Emerging role of leptin in rheumatoid arthritis","volume":"177","author":"Tian","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1007\/s10067-019-04533-1","article-title":"Ccl5 and related genes might be the potential diagnostic biomarkers for the therapeutic strategies of rheumatoid arthritis","volume":"38","author":"Huang","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2641098","DOI":"10.1155\/2019\/2641098","article-title":"Early peritoneal cc chemokine production correlates with divergent inflammatory phenotypes and susceptibility to experimental arthritis in mice","volume":"2019","author":"Rossato","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.4049\/jimmunol.175.4.2579","article-title":"Interaction between synovial inflammatory tissue and bone marrow in rheumatoid arthritis","volume":"175","author":"Redlich","year":"2005","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/art.10126","article-title":"Inflammation is preceded by tumor necrosis factor-dependent infiltration of mesenchymal cells in experimental arthritis","volume":"46","author":"Williams","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_65","first-page":"439","article-title":"Distinct alterations in lineage committed progenitor cells exist in the peripheral blood of patients with rheumatoid arthritis and primary sjogren\u2019s syndrome","volume":"23","author":"Sullivan","year":"1996","journal-title":"J. Rheumatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1093\/rheumatology\/38.9.854","article-title":"Establishment of nurse-like stromal cells from bone marrow of patients with rheumatoid arthritis: Indication of characteristic bone marrow microenvironment in patients with rheumatoid arthritis","volume":"38","author":"Tomita","year":"1999","journal-title":"Rheumatology (Oxford)"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1182\/blood.V99.5.1610","article-title":"Bone marrow progenitor cell reserve and function and stromal cell function are defective in rheumatoid arthritis: Evidence for a tumor necrosis factor alpha-mediated effect","volume":"99","author":"Papadaki","year":"2002","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1136\/ard.2007.076174","article-title":"Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis","volume":"67","author":"Kastrinaki","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"284215","DOI":"10.1155\/2015\/284215","article-title":"Mesenchymal stem cells from patients with rheumatoid arthritis display impaired function in inhibiting th17 cells","volume":"2015","author":"Sun","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1159\/000140679","article-title":"Chondrogenic potential of mesenchymal stem cells from patients with rheumatoid arthritis and osteoarthritis: Measurements in a microculture system","volume":"189","author":"Dudics","year":"2009","journal-title":"Cells Tissues Organs"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.yexcr.2016.12.009","article-title":"Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of beta-catenin","volume":"350","author":"Tong","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1365-2184.2011.00769.x","article-title":"Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells","volume":"44","author":"Huang","year":"2011","journal-title":"Cell Prolif."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/21\/5436\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:30:51Z","timestamp":1760189451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/21\/5436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,31]]},"references-count":72,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["ijms20215436"],"URL":"https:\/\/doi.org\/10.3390\/ijms20215436","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,31]]}}}