{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:05:15Z","timestamp":1792458315437,"version":"4.5.0"},"reference-count":137,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Rheumatoid arthritis is characterized by synovial inflammation and irreversible bone erosions, both highlighting the immense reciprocal relationship between the immune and bone systems, designed osteoimmunology two decades ago. Osteoclast-mediated resorption at the interface between synovium and bone is responsible for the articular bone erosions. The main triggers of this local bone resorption are autoantibodies directed against citrullinated proteins, as well as pro-inflammatory cytokines and the receptor activator of nuclear factor-\u03baB ligand, that regulate both the formation and activity of the osteoclast, as well as immune cell functions. In addition, local bone loss is due to the suppression of osteoblast-mediated bone formation and repair by inflammatory cytokines. Similarly, inflammation affects systemic bone remodeling in rheumatoid arthritis with the net increase in bone resorption, leading to systemic osteoporosis. This review summarizes the substantial progress that has been made in understanding the pathophysiology of systemic and local bone loss in rheumatoid arthritis.<\/jats:p>","DOI":"10.3390\/biom11010048","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T10:10:37Z","timestamp":1609409437000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Rheumatoid Arthritis in the View of Osteoimmunology"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6905-8735","authenticated-orcid":false,"given":"M\u00e9lanie","family":"Aur\u00e9al","sequence":"first","affiliation":[{"name":"INSERM UMR1033 LYOS, University of Lyon I, 69003 Lyon, France"},{"name":"Department of Rheumatology, Lyon Sud Hospital, 69310 Pierre-B\u00e9nite, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Machuca-Gayet","sequence":"additional","affiliation":[{"name":"INSERM UMR1033 LYOS, University of Lyon I, 69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Coury","sequence":"additional","affiliation":[{"name":"INSERM UMR1033 LYOS, University of Lyon I, 69003 Lyon, France"},{"name":"Department of Rheumatology, Lyon Sud Hospital, 69310 Pierre-B\u00e9nite, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1126\/science.177.4051.793","article-title":"Bone Resorbing Activity in Supernatant Fluid from Cultured Human Peripheral Blood Leukocytes","volume":"177","author":"Horton","year":"1972","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1056\/NEJM197411142912001","article-title":"Evidence for the secretion of an osteoclast stimulating factor in myeloma","volume":"291","author":"Mundy","year":"1974","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/35046196","article-title":"Bone versus immune system","volume":"408","author":"Arron","year":"2000","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1136\/ard.2010.132423","article-title":"A comparative study of periarticular bone lesions in rheumatoid arthritis and psoriatic arthritis","volume":"70","author":"Finzel","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1097\/BOR.0000000000000282","article-title":"MRI and ultrasound in rheumatoid arthritis","volume":"28","author":"Mathew","year":"2016","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1136\/annrheumdis-2012-202958","article-title":"Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies","volume":"73","author":"Kleyer","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1136\/ard.62.7.611","article-title":"Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis","volume":"62","author":"Lindqvist","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/art.1780330303","article-title":"Use of the radiograph to measure the course of rheumatoid arthritis","volume":"33","author":"Brower","year":"1990","journal-title":"Arthritis Rheum."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1002\/art.22117","article-title":"Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis","volume":"54","author":"Staa","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/1529-0131(200003)43:3<522::AID-ANR7>3.0.CO;2-Y","article-title":"Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: Results from 394 patients in the Oslo County Rheumatoid Arthritis register","volume":"43","author":"Haugeberg","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.berh.2016.08.010","article-title":"Imaging in osteoporosis in rheumatic diseases","volume":"30","author":"Mandl","year":"2016","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0149-2918(04)90001-X","article-title":"Secondary osteoporosis: Underlying disease and the risk for glucocorticoid-induced osteoporosis","volume":"26","author":"Boling","year":"2004","journal-title":"Clin. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nrg1122","article-title":"Genetic regulation of osteoclast development and function","volume":"4","author":"Teitelbaum","year":"2003","journal-title":"Nat. Rev. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1002\/art.1780270902","article-title":"Chondroclasts and osteoclasts at subchondral sites of erosion in the rheumatoid joint","volume":"27","author":"Bromley","year":"1984","journal-title":"Arthritis Rheum."},{"key":"ref_16","first-page":"9","article-title":"Identification of Cell Types Responsible for Bone Resorption in Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis","volume":"152","author":"Gravallese","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/35005552","article-title":"Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand","volume":"402","author":"Kong","year":"1999","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/S0002-9440(10)64417-3","article-title":"Osteoprotegerin Reduces Osteoclast Numbers and Prevents Bone Erosion in Collagen-Induced Arthritis","volume":"161","author":"Romas","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1002\/art.10607","article-title":"Increase in expression of receptor activator of nuclear factor B at sites of bone erosion correlates with progression of inflammation in evolving collagen-induced arthritis","volume":"46","author":"Lubberts","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1172\/JCI0215582","article-title":"Osteoclasts are essential for TNF-\u03b1\u2013mediated joint destruction","volume":"110","author":"Redlich","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/S0002-9440(10)63016-7","article-title":"TRANCE\/RANKL Knockout Mice Are Protected from Bone Erosion in a Serum Transfer Model of Arthritis","volume":"159","author":"Pettit","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1210\/endo-126-5-2733","article-title":"Identification of Committed Mononuclear Precursors for Osteoclast-Like Cells Formed in Long Term Human Marrow Cultures*","volume":"126","author":"Kurihara","year":"1990","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1136\/ard.55.11.816","article-title":"Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rheumatoid arthritis","volume":"55","author":"Fujikawa","year":"1996","journal-title":"Ann. Rheum. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1182\/blood-2004-01-0041","article-title":"Immature dendritic cell transdifferentiation into osteoclasts: A novel pathway sustained by the rheumatoid arthritis microenvironment","volume":"104","author":"Rivollier","year":"2004","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1002\/eji.200636534","article-title":"Murine dendritic cell transdifferentiation into osteoclasts is differentially regulated by innate and adaptive cytokines","volume":"37","author":"Speziani","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1051\/medsci\/2009253259","article-title":"Ost\u00e9oimmunologie: Une vision globale et int\u00e9gr\u00e9e du tissu squelettique et du syst\u00e8me immunitaire: Implication pour la recherche en rhumatologie","volume":"25","author":"Gallois","year":"2009","journal-title":"M\u00e9decine\/Sciences"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.4049\/jimmunol.177.5.3314","article-title":"Immune Interactions with CD4 + T Cells Promote the Development of Functional Osteoclasts from Murine CD11c + Dendritic Cells","volume":"177","author":"Alnaeeli","year":"2006","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1182\/blood-2008-01-132787","article-title":"Bone marrow microenvironment controls the in vivo differentiation of murine dendritic cells into osteoclasts","volume":"112","author":"Wakkach","year":"2008","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.4049\/jimmunol.0903560","article-title":"Dendritic Cell-Mediated In Vivo Bone Resorption","volume":"185","author":"Maitra","year":"2010","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1084\/jem.186.12.2075","article-title":"TRANCE (Tumor Necrosis Factor [TNF]-related Activation-induced Cytokine), a New TNF Family Member Predominantly Expressed in T cells, Is a Dendritic Cell\u2013specific Survival Factor","volume":"186","author":"Wong","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10905","DOI":"10.1073\/pnas.200294797","article-title":"Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene","volume":"97","author":"Kim","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00223-008-9196-4","article-title":"Infantile Malignant, Autosomal Recessive Osteopetrosis: The Rich and The Poor","volume":"84","author":"Villa","year":"2009","journal-title":"Calcif. Tissue Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1136\/ard.61.12.1047","article-title":"Receptor activator NF-\u03baB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: Semiquantitative and quantitative analysis","volume":"61","author":"Crotti","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1136\/annrheumdis-2014-207137","article-title":"RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation","volume":"75","author":"Danks","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1136\/ard.2009.121764","article-title":"Baseline RANKL:OPG ratio and markers of bone and cartilage degradation predict annual radiological progression over 11 years in rheumatoid arthritis","volume":"69","author":"Voskuyl","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0002-9440(10)63144-6","article-title":"Repair of local bone erosions and reversal of systemic bone loss upon therapy with anti-tumor necrosis factor in combination with osteoprotegerin or parathyroid hormone in tumor necrosis factor-mediated arthritis","volume":"164","author":"Redlich","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1136\/annrheumdis-2015-208052","article-title":"Effect of denosumab on Japanese patients with rheumatoid arthritis: A dose\u2013response study of AMG 162 ( D enosumab) in patients with R heumato I d arthritis on methotrexate to V alidate inhibitory effect on bone E rosion (DRIVE)\u2014A 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial","volume":"75","author":"Takeuchi","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1002\/art.23417","article-title":"Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: A twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial","volume":"58","author":"Cohen","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1136\/annrheumdis-2018-214827","article-title":"Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): A randomised, double-blind, placebo-controlled phase 3 trial","volume":"78","author":"Takeuchi","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1084\/jem.20112012","article-title":"Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis","volume":"209","author":"Nikitopoulou","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"David, M., Wannecq, E., Descotes, F., Jansen, S., Deux, B., Ribeiro, J., Serre, C.-M., Gr\u00e8s, S., Bendriss-Vermare, N., and Bollen, M. (2010). Cancer Cell Expression of Autotaxin Controls Bone Metastasis Formation in Mouse through Lysophosphatidic Acid-Dependent Activation of Osteoclasts. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009741"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6551","DOI":"10.1074\/jbc.M113.533232","article-title":"Lysophosphatidic Acid Receptor Type 1 (LPA 1 ) Plays a Functional Role in Osteoclast Differentiation and Bone Resorption Activity","volume":"289","author":"David","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6158","DOI":"10.1073\/pnas.0401602101","article-title":"The immunomodulatory adapter proteins DAP12 and Fc receptor -chain (FcR ) regulate development of functional osteoclasts through the Syk tyrosine kinase","volume":"101","author":"Mocsai","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/nature02444","article-title":"Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis","volume":"428","author":"Koga","year":"2004","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R245","DOI":"10.1186\/ar4088","article-title":"The immunoreceptor tyrosine-based activation motif (ITAM) -related factors are increased in synovial tissue and vasculature of rheumatoid arthritic joints","volume":"14","author":"Crotti","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1002\/art.23943","article-title":"Induction of osteoclast-associated receptor, a key osteoclast costimulation molecule, in rheumatoid arthritis","volume":"58","author":"Herman","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.cell.2007.12.037","article-title":"Tyrosine Kinases Btk and Tec Regulate Osteoclast Differentiation by Linking RANK and ITAM Signals","volume":"132","author":"Shinohara","year":"2008","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bone.2013.11.025","article-title":"The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss","volume":"60","author":"Shinohara","year":"2014","journal-title":"Bone"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/rheumatology\/ker257","article-title":"Intrinsic danger: Activation of Toll-like receptors in rheumatoid arthritis","volume":"51","author":"Goh","year":"2012","journal-title":"Rheumatol. Oxf. Engl."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"810","DOI":"10.3899\/jrheum.100732","article-title":"Expression of Toll-like receptors and their signaling pathways in rheumatoid synovitis","volume":"38","author":"Tamaki","year":"2011","journal-title":"J. Rheumatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7223","DOI":"10.4049\/jimmunol.0900072","article-title":"Inhibition of RANK expression and osteoclastogenesis by TLRs and IFN-gamma in human osteoclast precursors","volume":"183","author":"Ji","year":"2009","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1084\/jem.20061775","article-title":"Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction","volume":"203","author":"Sato","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1172\/JCI5703","article-title":"IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis","volume":"103","author":"Kotake","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.immuni.2008.07.018","article-title":"Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction","volume":"29","author":"Ogura","year":"2008","journal-title":"Immunity"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.4049\/jimmunol.160.7.3513","article-title":"IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages","volume":"160","author":"Jovanovic","year":"1998","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"52ra72","DOI":"10.1126\/scitranslmed.3001107","article-title":"Effects of AIN457, a Fully Human Antibody to Interleukin-17A, on Psoriasis, Rheumatoid Arthritis, and Uveitis","volume":"2","author":"Hueber","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1136\/annrheumdis-2012-201601","article-title":"Efficacy and safety of secukinumab in patients with rheumatoid arthritis: A phase II, dose-finding, double-blind, randomised, placebo controlled study","volume":"72","author":"Genovese","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"495","DOI":"10.3899\/jrheum.150117","article-title":"Efficacy and Safety of Subcutaneous and Intravenous Loading Dose Regimens of Secukinumab in Patients with Active Rheumatoid Arthritis: Results from a Randomized Phase II Study","volume":"43","author":"Tlustochowicz","year":"2016","journal-title":"J. Rheumatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1002\/art.40070","article-title":"Secukinumab in Active Rheumatoid Arthritis: A Phase III Randomized, Double-Blind, Active Comparator\u2013 and Placebo-Controlled Study","volume":"69","author":"Blanco","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/35046102","article-title":"T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma","volume":"408","author":"Takayanagi","year":"2000","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1136\/ard.2007.080713","article-title":"CTLA-4 directly inhibits osteoclast formation","volume":"67","author":"Axmann","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1136\/ard.2007.086066","article-title":"Activated CD4 + CD25 + regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis","volume":"68","author":"Kelchtermans","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7238","DOI":"10.4049\/jimmunol.0903841","article-title":"Regulatory T cells protect from local and systemic bone destruction in arthritis","volume":"184","author":"Zaiss","year":"2010","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"19396","DOI":"10.1073\/pnas.0806855105","article-title":"Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritis","volume":"105","author":"Jury","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"R335","DOI":"10.1186\/ar1192","article-title":"CD25brightCD4+regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease","volume":"6","author":"Cao","year":"2004","journal-title":"Arthritis Res. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1093\/rheumatology\/kev403","article-title":"Abatacept (CTLA-4Ig) treatment reduces T cell apoptosis and regulatory T cell suppression in patients with rheumatoid arthritis","volume":"55","author":"Bonelli","year":"2016","journal-title":"Rheumatology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1093\/rheumatology\/kev443","article-title":"Striking difference of periarticular bone density change in early psoriatic arthritis and rheumatoid arthritis following anti-rheumatic treatment as measured by digital X-ray radiogrammetry","volume":"55","author":"Szentpetery","year":"2016","journal-title":"Rheumatology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/s10875-011-9527-5","article-title":"CTLA-4-Ig therapy diminishes the frequency but enhances the function of Treg cells in patients with rheumatoid arthritis","volume":"31","author":"Baranda","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"ref_69","first-page":"259","article-title":"Paucity of radiographic progression in rheumatoid arthritis treated with methotrexate as the first disease modifying antirheumatic drug","volume":"26","author":"Rich","year":"1999","journal-title":"J. Rheumatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1002\/j.1460-2075.1991.tb04978.x","article-title":"Transgenic mice expressing human tumour necrosis factor: A predictive genetic model of arthritis","volume":"10","author":"Keffer","year":"1991","journal-title":"EMBO J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1002\/art.23653","article-title":"Cytokine-controlled RANKL and osteoprotegerin expression by human and mouse synovial fibroblasts: Fibroblast-mediated pathologic bone resorption","volume":"58","author":"Radacs","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1093\/rheumatology\/ken363","article-title":"IL-6 trans-signalling directly induces RANKL on fibroblast-like synovial cells and is involved in RANKL induction by TNF-alpha and IL-17","volume":"47","author":"Hashizume","year":"2008","journal-title":"Rheumatol. Oxf. Engl."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1172\/JCI11176","article-title":"TNF-\u03b1 induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand","volume":"106","author":"Lam","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"11846","DOI":"10.1074\/jbc.M512624200","article-title":"Tumor Necrosis Factor-\u03b1 Increases Circulating Osteoclast Precursor Numbers by Promoting Their Proliferation and Differentiation in the Bone Marrow through Up-regulation of c-Fms Expression","volume":"281","author":"Yao","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1002\/art.37902","article-title":"Inhibition of Connective Tissue Growth Factor Ameliorates Disease in a Murine Model of Rheumatoid Arthritis: Blockade of CTGF Ameliorates Arthritis in Mice With CIA","volume":"65","author":"Nozawa","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"R174","DOI":"10.1186\/ar2863","article-title":"Connective tissue growth factor promotes articular damage by increased osteoclastogenesis in patients with rheumatoid arthritis","volume":"11","author":"Nozawa","year":"2009","journal-title":"Arthritis Res. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nature04753","article-title":"Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells","volume":"441","author":"Bettelli","year":"2006","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1172\/JCI200523394","article-title":"IL-1 mediates TNF-induced osteoclastogenesis","volume":"115","author":"Wei","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1006\/excr.1998.4320","article-title":"Interleukin 1 induces multinucleation and bone-resorbing activity of osteoclasts in the absence of osteoblasts\/stromal cells","volume":"247","author":"Jimi","year":"1999","journal-title":"Exp. Cell Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1136\/ard.2005.044198","article-title":"Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NF B ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis","volume":"65","author":"Vis","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1136\/ard.2006.068064","article-title":"Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): Evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab","volume":"66","author":"Nishimoto","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/1529-0131(200005)43:5<1001::AID-ANR7>3.0.CO;2-P","article-title":"A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: Radiologic progression and correlation of Genant and Larsen scores","volume":"43","author":"Jiang","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1136\/ard.2009.124537","article-title":"Epitope spreading of the anti-citrullinated protein antibody response occurs before disease onset and is associated with the disease course of early arthritis","volume":"69","author":"Onnekink","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1136\/ard.2010.135723","article-title":"Bone metabolism is altered in preclinical rheumatoid arthritis","volume":"70","author":"Nielen","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1136\/annrheumdis-2011-200990","article-title":"EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: Report from the Study Group for Risk Factors for Rheumatoid Arthritis","volume":"71","author":"Gerlag","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1172\/JCI60975","article-title":"Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin","volume":"122","author":"Harre","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1136\/ard.2010.142091","article-title":"Fc\u03b3 receptor profile of monocytes and macrophages from rheumatoid arthritis patients and their response to immune complexes formed with autoantibodies to citrullinated proteins","volume":"70","author":"Laurent","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1002\/art.23284","article-title":"Induction of macrophage secretion of tumor necrosis factor alpha through Fcgamma receptor IIa engagement by rheumatoid arthritis-specific autoantibodies to citrullinated proteins complexed with fibrinogen","volume":"58","author":"Clavel","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1002\/art.27386","article-title":"Anti-citrullinated protein antibodies bind surface-expressed citrullinated Grp78 on monocyte\/macrophages and stimulate tumor necrosis factor \u03b1 production","volume":"62","author":"Lu","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"10729","DOI":"10.1073\/pnas.1301001110","article-title":"Inflammatory monocytes and Fc receptor IV on osteoclasts are critical for bone destruction during inflammatory arthritis in mice","volume":"110","author":"Seeling","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1136\/annrheumdis-2015-208093","article-title":"Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss","volume":"75","author":"Krishnamurthy","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"(2019). Correction: Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann. Rheum. Dis., 78, 866.","DOI":"10.1136\/annrheumdis-2015-208093corr1"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"(2019). Correction: Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann. Rheum. Dis., 78, 865.","DOI":"10.1136\/annrheumdis-2015-208094corr1"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1136\/annrheumdis-2015-208094","article-title":"Autoantibodies to citrullinated proteins may induce joint pain independent of inflammation","volume":"75","author":"Wigerblad","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/316452a0","article-title":"Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG","volume":"316","author":"Parekh","year":"1985","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/rheumatology\/33.1.36","article-title":"Early agalactosylation of IgG is associated with a more progressive disease course in patients with rheumatoid arthritis: Results of a follow-up study","volume":"33","author":"Rook","year":"1994","journal-title":"Br. J. Rheumatol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3109\/07853899609033129","article-title":"Changes in agalactosyl IgG levels correlate with radiological progression in early rheumatoid arthritis","volume":"28","author":"Lacki","year":"1996","journal-title":"Ann. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/jcla.20191","article-title":"Effect of infliximab on the glycosylation of IgG of patients with rheumatoid arthritis","volume":"21","author":"Croce","year":"2007","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s10067-006-0370-7","article-title":"The changes in monosaccharide composition of immunoglobulin G in the course of rheumatoid arthritis","volume":"26","author":"Klimiuk","year":"2007","journal-title":"Clin. Rheumatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s10719-006-5409-0","article-title":"Galactosylation of IgG from rheumatoid arthritis (RA) patients--changes during therapy","volume":"23","author":"Pasek","year":"2006","journal-title":"Glycoconj. J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"6651","DOI":"10.1038\/ncomms7651","article-title":"Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss","volume":"6","author":"Harre","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev.immunol.25.022106.141702","article-title":"The Impact of Glycosylation on the Biological Function and Structure of Human Immunoglobulins","volume":"25","author":"Arnold","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1136\/annrheumdis-2013-203565","article-title":"Anti-citrullinated protein antibodies acquire a pro-inflammatory Fc glycosylation phenotype prior to the onset of rheumatoid arthritis","volume":"74","author":"Rombouts","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/ni.3579","article-title":"Regulation of autoantibody activity by the IL-23\u2013TH17 axis determines the onset of autoimmune disease","volume":"18","author":"Pfeifle","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.semarthrit.2016.09.011","article-title":"Effects of DMARDs on citrullinated peptide autoantibody levels in RA patients\u2014A longitudinal analysis","volume":"46","author":"Wunderlich","year":"2017","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"R159","DOI":"10.1186\/ar4342","article-title":"Anti-citrullinated peptide autoantibodies, human leukocyte antigen shared epitope and risk of future rheumatoid arthritis: A nested case\u2013control study","volume":"15","author":"Arkema","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"11193","DOI":"10.1073\/pnas.1019536108","article-title":"MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis","volume":"108","author":"Alivernini","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1002\/art.30281","article-title":"Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice","volume":"63","author":"Bonelli","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.4049\/jimmunol.1600360","article-title":"MicroRNA-17 Suppresses TNF-\u03b1 Signaling by Interfering with TRAF2 and cIAP2 Association in Rheumatoid Arthritis Synovial Fibroblasts","volume":"197","author":"Akhtar","year":"2016","journal-title":"J. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1136\/annrheumdis-2014-206417","article-title":"MicroRNA-124 inhibits the progression of adjuvant-induced arthritis in rats","volume":"75","author":"Nakamachi","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/art.38190","article-title":"Dual Role of Autophagy in Stress-Induced Cell Death in Rheumatoid Arthritis Synovial Fibroblasts: Autophagy in RA","volume":"66","author":"Kato","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/annrheumdis-2012-201671","article-title":"Autophagy regulates TNF\u03b1-mediated joint destruction in experimental arthritis","volume":"72","author":"Lin","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1369\/0022155414551367","article-title":"The Adaptor Protein p62 Is Involved in RANKL-induced Autophagy and Osteoclastogenesis","volume":"62","author":"Li","year":"2014","journal-title":"J. Histochem. Cytochem."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Montaseri, A., Giampietri, C., Rossi, M., Riccioli, A., Del Fattore, A., and Filippini, A. (2020). The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function. Biomolecules, 10.","DOI":"10.3390\/biom10101398"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1002\/art.41290","article-title":"Protective Role of Optineurin Against Joint Destruction in Rheumatoid Arthritis Synovial Fibroblasts","volume":"72","author":"Lee","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1136\/annrheumdis-2011-201075","article-title":"Interleukin-6 receptor blockade induces limited repair of bone erosions in rheumatoid arthritis: A micro CT study","volume":"72","author":"Finzel","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1002\/art.40156","article-title":"Effects of Teriparatide on Joint Erosions in Rheumatoid Arthritis: A Randomized Controlled Trial: TERIPARATIDE IN RA","volume":"69","author":"Solomon","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.3074","article-title":"WNT signaling in bone homeostasis and disease: From human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nat. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.str.2011.07.005","article-title":"Wnt Antagonists Bind through a Short Peptide to the First \u03b2-Propeller Domain of LRP5\/6","volume":"19","author":"Bourhis","year":"2011","journal-title":"Structure"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nm1538","article-title":"Dickkopf-1 is a master regulator of joint remodeling","volume":"13","author":"Diarra","year":"2007","journal-title":"Nat. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"330ra35","DOI":"10.1126\/scitranslmed.aac4351","article-title":"Sclerostin inhibition promotes TNF-dependent inflammatory joint destruction","volume":"8","author":"Wehmeyer","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.intimp.2018.04.019","article-title":"The serum level of Dickkopf-1 in patients with rheumatoid arthritis: A systematic review and meta-analysis","volume":"59","author":"Ma","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"211ra158","DOI":"10.1126\/scitranslmed.3006627","article-title":"Sclerostin inhibition reverses skeletal fragility in an Lrp5-deficient mouse model of OPPG syndrome","volume":"5","author":"Kedlaya","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1002\/jbmr.14","article-title":"Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength","volume":"25","author":"Ominsky","year":"2010","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","article-title":"Romosozumab Treatment in Postmenopausal Women with Osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"R125","DOI":"10.1186\/ar4305","article-title":"Effect of sclerostin-neutralising antibody on periarticular and systemic bone in a murine model of rheumatoid arthritis: A microCT study","volume":"15","author":"Marenzana","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"43-56.e21","DOI":"10.1016\/j.cell.2018.07.029","article-title":"Identification of the Human Skeletal Stem Cell","volume":"175","author":"Chan","year":"2018","journal-title":"Cell"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/jbmr.3005","article-title":"Synovium-Derived MicroRNAs Regulate Bone Pathways in Rheumatoid Arthritis: Synovium-Derived miRNAs Regulate Bone Pathways in Rheumatoid Arthritis","volume":"32","author":"Maeda","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s13075-018-1703-z","article-title":"Osteogenic differentiation of fibroblast-like synovial cells in rheumatoid arthritis is induced by microRNA-218 through a ROBO\/Slit pathway","volume":"20","author":"Iwamoto","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41413-018-0035-6","article-title":"RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation","volume":"6","author":"Chen","year":"2018","journal-title":"Bone Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/art.39489","article-title":"Production of RANKL by Memory B Cells: A Link Between B Cells and Bone Erosion in Rheumatoid Arthritis","volume":"68","author":"Meednu","year":"2016","journal-title":"Arthritis Rheumatol. Hoboken NJ"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"5127","DOI":"10.1038\/s41467-018-07626-8","article-title":"B cells inhibit bone formation in rheumatoid arthritis by suppressing osteoblast differentiation","volume":"9","author":"Sun","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"266","DOI":"10.3389\/fimmu.2019.00266","article-title":"Targeting Mesenchymal Stromal Cells\/Pericytes (MSCs) With Pulsed Electromagnetic Field (PEMF) Has the Potential to Treat Rheumatoid Arthritis","volume":"10","author":"Ross","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1053\/apmr.2001.24309","article-title":"Two configurations of static magnetic fields for treating rheumatoid arthritis of the knee: A double-blind clinical trial","volume":"82","author":"Segal","year":"2001","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1182\/blood-2014-04-568683","article-title":"Interaction of platelet-derived autotaxin with tumor integrin aVb3 controls metastasis of breast cancer cells to bone","volume":"124","author":"Leblanc","year":"2014","journal-title":"Blood"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1097\/MOT.0000000000000158","article-title":"Mesenchymal stromal cells for prevention and treatment of graft-versus-host disease: Successes and hurdles","volume":"20","author":"Introna","year":"2015","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref_137","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."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/1\/48\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:48:34Z","timestamp":1760179714000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/1\/48"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,31]]},"references-count":137,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["biom11010048"],"URL":"https:\/\/doi.org\/10.3390\/biom11010048","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,31]]}}}