{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:02:55Z","timestamp":1783728175900,"version":"3.55.0"},"reference-count":75,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T00:00:00Z","timestamp":1571097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The synovium exercises its main function in joint homeostasis through the secretion of factors (such as lubricin and hyaluronic acid) that are critical for the joint lubrication and function. The main synovium cell components are fibroblast-like synoviocytes, mesenchymal stromal\/stem cells and macrophage-like synovial cells. In the synovium, cells of mesenchymal origin modulate local inflammation and fibrosis, and interact with different fibroblast subtypes and with resident macrophages. In pathologic conditions, such as rheumatoid arthritis, fibroblast-like synoviocytes proliferate abnormally, recruit mesenchymal stem cells from subchondral bone marrow, and influence immune cell activity through epigenetic and metabolic adaptations. The resulting synovial hyperplasia leads to secondary cartilage destruction, joint swelling, and pain. In the present review, we summarize recent findings on the molecular signature and the roles of stromal cells during synovial pannus formation and rheumatoid arthritis progression.<\/jats:p>","DOI":"10.3390\/cells8101257","type":"journal-article","created":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T03:32:54Z","timestamp":1571196774000},"page":"1257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Where to Stand with Stromal Cells and Chronic Synovitis in Rheumatoid Arthritis?"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5991-3945","authenticated-orcid":false,"given":"Jean-Marc","family":"Brondello","sequence":"first","affiliation":[{"name":"IRMB, Univ Montpellier, INSERM, F-34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farida","family":"Djouad","sequence":"additional","affiliation":[{"name":"IRMB, Univ Montpellier, INSERM, F-34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"IRMB, Univ Montpellier, INSERM, F-34295 Montpellier, France"},{"name":"CHU Montpellier, F-34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,15]]},"reference":[{"key":"ref_1","first-page":"010409","article-title":"Prevalence of rheumatoid arthritis in low- and middle-income countries: A systematic review and analysis","volume":"5","author":"Rudan","year":"2015","journal-title":"J. Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/nrrheum.2016.119","article-title":"Deregulation and therapeutic potential of microRNAs in arthritic diseases","volume":"12","author":"Vicente","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","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. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41586-019-1471-1","article-title":"Locally renewing resident synovial macrophages provide a protective barrier for the joint","volume":"572","author":"Culemann","year":"2019","journal-title":"Nature"},{"key":"ref_5","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_6","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_7","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.molmed.2010.07.004","article-title":"Rheumatoid arthritis progression mediated by activated synovial fibroblasts","volume":"16","author":"Neumann","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_8","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_9","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 Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.arthro.2013.02.026","article-title":"Synovial membrane-derived mesenchymal stem cells supported by platelet-rich plasma can repair osteochondral defects in a rabbit model","volume":"29","author":"Lee","year":"2013","journal-title":"Arthroscopy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/cei.13149","article-title":"Stroma: The forgotten cells of innate immune memory","volume":"193","author":"Crowley","year":"2018","journal-title":"Clin. Exp. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"382","DOI":"10.4161\/auto.27345","article-title":"The glycolytic enzyme PFKFB3\/phosphofructokinase regulates autophagy","volume":"10","author":"Yang","year":"2014","journal-title":"Autophagy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nrrheum.2017.49","article-title":"Immunometabolism in early and late stages of rheumatoid arthritis","volume":"13","author":"Weyand","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1002\/art.40504","article-title":"Review: Synovial Cell Metabolism and Chronic Inflammation in Rheumatoid Arthritis","volume":"70","author":"Falconer","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_15","unstructured":"Patricia, L.-C., Hernandez, F.J., Djouad, F., Luque-Campos, N., Caceido, A., Kremer, S.C., Brondello, J., Vignais, M., P\u00e8ne, J., and Jorgensen, C. (2019). Mesenchymal stem cell repression of Th17 cells is triggered by mitochondrial transfer. Stem Cell Res. Ther., in press."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.exger.2017.10.027","article-title":"DNA damage, metabolism and aging in pro-inflammatory T cells: Rheumatoid arthritis as a model system","volume":"105","author":"Li","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R1304","DOI":"10.1186\/ar1827","article-title":"Transcriptional profiles discriminate bone marrow-derived and synovium-derived mesenchymal stem cells","volume":"7","author":"Djouad","year":"2005","journal-title":"Arthritis Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1002\/1529-0131(200108)44:8<1928::AID-ART331>3.0.CO;2-P","article-title":"Multipotent mesenchymal stem cells from adult human synovial membrane","volume":"44","author":"Tylzanowski","year":"2001","journal-title":"Arthritis Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/1529-0131(200101)44:1<85::AID-ANR12>3.0.CO;2-6","article-title":"Human periosteum-derived cells maintain phenotypic stability and chondrogenic potential throughout expansion regardless of donor age","volume":"44","author":"Luyten","year":"2001","journal-title":"Arthritis Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1002\/art.21212","article-title":"Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source","volume":"52","author":"Sakaguchi","year":"2005","journal-title":"Arthritis Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nrrheum.2017.182","article-title":"Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis","volume":"13","author":"McGonagle","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ydbio.2008.01.012","article-title":"A distinct cohort of progenitor cells participates in synovial joint and articular cartilage formation during mouse limb skeletogenesis","volume":"316","author":"Koyama","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s12663-018-1102-7","article-title":"Arthroscopic Management of Synovial Chondromatosis of the Temporomandibular Joint. Case Series and Systematic Review","volume":"17","author":"Brabyn","year":"2018","journal-title":"J. Maxillofac. Oral Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17432","DOI":"10.1073\/pnas.0607939103","article-title":"An essential role of NF-kappaB in the \u201ctumor-like\u201d phenotype of arthritic synoviocytes","volume":"103","author":"Li","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"121","DOI":"10.22203\/eCM.v020a11","article-title":"Mesenchymal stem cells: A perspective from in vitro cultures to in vivo migration and niches","volume":"20","author":"Augello","year":"2010","journal-title":"Eur. Cell Mater."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.4049\/jimmunol.1402900","article-title":"Placental growth factor-1 and -2 induce hyperplasia and invasiveness of primary rheumatoid synoviocytes","volume":"194","author":"Yoo","year":"2015","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.it.2004.11.014","article-title":"A stromal address code defined by fibroblasts","volume":"26","author":"Parsonage","year":"2005","journal-title":"Trends Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s13075-016-1060-8","article-title":"Bone marrow contribution to synovial hyperplasia following joint surface injury","volume":"18","author":"Sergijenko","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13075-016-0966-5","article-title":"CD271(+) stromal cells expand in arthritic synovium and exhibit a proinflammatory phenotype","volume":"18","author":"Fare","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1002\/art.30234","article-title":"Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo","volume":"63","author":"Kurth","year":"2011","journal-title":"Arthritis Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2106\/00004623-199605000-00012","article-title":"Repair of partial-thickness defects in articular cartilage: Cell recruitment from the synovial membrane","volume":"78","author":"Hunziker","year":"1996","journal-title":"J. Bone Joint Surg. Am."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nrrheum.2012.190","article-title":"Duality of fibroblast-like synoviocytes in RA: Passive responders and imprinted aggressors","volume":"9","author":"Bottini","year":"2013","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1136\/annrheumdis-2018-214783","article-title":"TNF-induced inflammatory genes escape repression in fibroblast-like synoviocytes: Transcriptomic and epigenomic analysis","volume":"78","author":"Loh","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1038\/s41467-018-04310-9","article-title":"Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes","volume":"9","author":"Ai","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1172\/JCI85632","article-title":"Chondrocyte clocks make cartilage time-sensitive material","volume":"126","author":"Doody","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nrrheum.2017.96","article-title":"Why location matters-site-specific factors in rheumatic diseases","volume":"13","author":"Ospelt","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1084\/jem.20071397","article-title":"Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model","volume":"204","author":"Hirota","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.rdc.2010.02.006","article-title":"Targeting IL-17 and Th17 cells in rheumatoid arthritis","volume":"36","author":"Sarkar","year":"2010","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cei.12382","article-title":"Enhancement of T cell recruitment and infiltration into tumours","volume":"178","author":"Oelkrug","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3389\/fimmu.2015.00384","article-title":"T Cell Migration in Rheumatoid Arthritis","volume":"6","author":"Mellado","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1046\/j.0300-9475.2002.01036.x","article-title":"Association of antigen specificity and migratory capacity of memory T cells in rheumatoid arthritis","volume":"55","author":"Shadidi","year":"2002","journal-title":"Scand. J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.0105-2896.2009.00859.x","article-title":"Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis","volume":"233","author":"Bartok","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8463","DOI":"10.4049\/jimmunol.179.12.8463","article-title":"Blockade of chemokine receptor CXCR3 inhibits T cell recruitment to inflamed joints and decreases the severity of adjuvant arthritis","volume":"179","author":"Mohan","year":"2007","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1046\/j.1365-2249.2003.02126.x","article-title":"Regulation of CCR5 expression and MIP-1alpha production in CD4+ T cells from patients with rheumatoid arthritis","volume":"132","author":"Wang","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1136\/ard.58.9.573","article-title":"Tumour necrosis factor alpha stimulated rheumatoid synovial microvascular endothelial cells exhibit increased shear rate dependent leucocyte adhesion in vitro","volume":"58","author":"Abbot","year":"1999","journal-title":"Ann. Rheum. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.3389\/fimmu.2017.01627","article-title":"Sphingosine-1-Phosphate Promotes the Persistence of Activated CD4 T Cells in Inflamed Sites","volume":"8","author":"Jaigirdar","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/art.21668","article-title":"Sphingosine 1-phosphate\/sphingosine 1-phosphate receptor 1 signaling in rheumatoid synovium: Regulation of synovial proliferation and inflammatory gene expression","volume":"54","author":"Kitano","year":"2006","journal-title":"Arthritis Rheumatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"424","DOI":"10.2478\/s11658-009-0009-1","article-title":"Chronic increases in sphingosine kinase-1 activity induce a pro-inflammatory, pro-angiogenic phenotype in endothelial cells","volume":"14","author":"Limaye","year":"2009","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.4049\/jimmunol.169.4.1760","article-title":"Fibroblast-like synoviocytes from rheumatoid arthritis patients express functional IL-15 receptor complex: Endogenous IL-15 in autocrine fashion enhances cell proliferation and expression of Bcl-x(L) and Bcl-2","volume":"169","author":"Kurowska","year":"2002","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"R157","DOI":"10.1186\/ar2052","article-title":"PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53","volume":"8","author":"You","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1002\/art.39641","article-title":"Reduced DICER1 Expression Bestows Rheumatoid Arthritis Synoviocytes Proinflammatory Properties and Resistance to Apoptotic Stimuli","volume":"68","author":"Alsaleh","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.3389\/fimmu.2018.01647","article-title":"DICER1: A Key Player in Rheumatoid Arthritis, at the Crossroads of Cellular Stress, Innate Immunity, and Chronic Inflammation in Aging","volume":"9","author":"Mariotte","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R33","DOI":"10.1186\/ar2941","article-title":"Akt activity protects rheumatoid synovial fibroblasts from Fas-induced apoptosis by inhibition of Bid cleavage","volume":"12","author":"Garcia","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1002\/art.20453","article-title":"Down-regulation of FLIP sensitizes rheumatoid synovial fibroblasts to Fas-mediated apoptosis","volume":"50","author":"Palao","year":"2004","journal-title":"Arthritis Rheumatol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yang, X.Y., Zheng, K.D., Lin, K., Zheng, G., Zou, H., Wang, J.M., Lin, Y.Y., Chuka, C.M., Ge, R.S., and Zhai, W. (2015). Energy Metabolism Disorder as a Contributing Factor of Rheumatoid Arthritis: A Comparative Proteomic and Metabolomic Study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132695"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nature16187","article-title":"Autophagy maintains stemness by preventing senescence","volume":"529","author":"Perdiguero","year":"2016","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s00109-008-0365-8","article-title":"Human rheumatoid synoviocytes express functional P2 \u00d7 7 receptors","volume":"86","author":"Caporali","year":"2008","journal-title":"J. Mol. Med. (Berl)"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6917941","DOI":"10.1155\/2017\/6917941","article-title":"Cell Connections by Tunneling Nanotubes: Effects of Mitochondrial Trafficking on Target. Cell Metabolism, Homeostasis, and Response to Therapy","volume":"2017","author":"Vignais","year":"2017","journal-title":"Stem. Cells Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1002\/art.21927","article-title":"Direct modulation of rheumatoid inflammatory mediator expression in retinoblastoma protein-dependent and -independent pathways by cyclin-dependent kinase 4\/6","volume":"54","author":"Nonomura","year":"2006","journal-title":"Arthritis Rheumatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.4049\/jimmunol.180.3.1954","article-title":"Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-dependent kinase inhibitors","volume":"180","author":"Sekine","year":"2008","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7246","DOI":"10.4049\/jimmunol.165.12.7246","article-title":"Adenoviral transfer of cyclin-dependent kinase inhibitor genes suppresses collagen-induced arthritis in mice","volume":"165","author":"Nasu","year":"2000","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/10480","article-title":"Induction of the p16INK4a senescence gene as a new therapeutic strategy for the treatment of rheumatoid arthritis","volume":"5","author":"Taniguchi","year":"1999","journal-title":"Nat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cell.2017.05.015","article-title":"Senescence in Health and Disease","volume":"169","author":"He","year":"2017","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/nrd.2017.116","article-title":"Senescent cells: An emerging target for diseases of ageing","volume":"16","author":"Childs","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/acel.12455","article-title":"Cellular senescence impact on immune cell fate and function","volume":"15","author":"Vicente","year":"2016","journal-title":"Aging Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1172\/JCI95147","article-title":"Senescent cells and osteoarthritis: A painful connection","volume":"128","author":"Jeon","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bcp.2019.03.017","article-title":"Seno-suppressive molecules as new therapeutic perspectives in rheumatic diseases","volume":"165","author":"Tachikart","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1002\/art.23287","article-title":"Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis","volume":"58","author":"Colmegna","year":"2008","journal-title":"Arthritis Rheumatol."},{"key":"ref_71","first-page":"524","article-title":"Telomere dysfunction, autoimmunity and aging","volume":"2","author":"Hohensinner","year":"2011","journal-title":"Aging Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1196\/annals.1358.022","article-title":"Costimulatory pathways in rheumatoid synovitis and T-cell senescence","volume":"1062","author":"Goronzy","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.4049\/jimmunol.0803449","article-title":"Modulation of T lymphocyte replicative senescence via TNF-{alpha} inhibition: Role of caspase-3","volume":"182","author":"Parish","year":"2009","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJMoa1109071","article-title":"Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis","volume":"367","author":"Fleischmann","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/art.39953","article-title":"Baricitinib, Methotrexate, or Combination in Patients with Rheumatoid Arthritis and No or Limited Prior Disease-Modifying Antirheumatic Drug Treatment","volume":"69","author":"Fleischmann","year":"2017","journal-title":"Arthritis Rheumatol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/10\/1257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:26:30Z","timestamp":1760189190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/10\/1257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,15]]},"references-count":75,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["cells8101257"],"URL":"https:\/\/doi.org\/10.3390\/cells8101257","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,15]]}}}