{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:39:05Z","timestamp":1790692745614,"version":"4.1.0"},"reference-count":146,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments for decades, owing to their anti-inflammatory, immunomodulatory, and regenerative properties. With high expectations, many ongoing clinical trials are investigating the safety and efficacy of MSC therapies to treat arthritic diseases. Studies on osteoarthritis (OA) have shown positive clinical outcomes, with improved joint function, pain level, and quality of life. In addition, few clinical MSC trials conducted on rheumatoid arthritis (RA) patients have also displayed some optimistic outlook. The largely positive outcomes in clinical trials without severe side effects establish MSCs as promising tools for arthritis treatment. However, further research is required to investigate its applicability in clinical settings. This review discusses the most recent advances in clinical studies on MSC therapies for OA and RA.<\/jats:p>","DOI":"10.3389\/fimmu.2021.631291","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T05:55:58Z","timestamp":1615182958000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":130,"title":["Recent Developments in Clinical Applications of Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis and Osteoarthritis"],"prefix":"10.3389","volume":"12","author":[{"given":"Joel Jihwan","family":"Hwang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeri Alice","family":"Rim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoojun","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hyeon","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"B1","first-page":"3","article-title":"[Osteogenesis in transplants of bone marrow cells]","volume":"56","author":"Fridenshtein","year":"1969","journal-title":"Arkh Anat Gistol Embriol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41536-019-0083-6","article-title":"Mesenchymal stem cell perspective: cell biology to clinical progress","volume":"4","author":"Pittenger","year":"2019","journal-title":"NPJ Regen Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1111\/j.1365-2184.1987.tb01309.x","article-title":"Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers","volume":"20","author":"Friedenstein","year":"1987","journal-title":"Cell Tissue Kinet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1111\/j.1365-2184.1970.tb00347.x","article-title":"The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells","volume":"3","author":"Friedenstein","year":"1970","journal-title":"Cell Tissue Kinet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3389\/fbioe.2020.00148","article-title":"Five decades later, are mesenchymal stem cells still relevant?","volume":"8","author":"Gomez-Salazar","year":"2020","journal-title":"Front Bioeng Biotechnol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1002\/jor.1100090504","article-title":"Mesenchymal stem cells","volume":"9","author":"Caplan","year":"1991","journal-title":"J Orthop Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1002\/sctm.17-0051","article-title":"Mesenchymal stem cells: time to change the name!","volume":"6","author":"Caplan","year":"2017","journal-title":"Stem Cells Transl Med."},{"key":"B8","doi-asserted-by":"publisher","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":"B9","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/j.jcyt.2019.08.002","article-title":"Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy [ISCT(R)] mesenchymal stromal cell committee position statement on nomenclature","volume":"21","author":"Viswanathan","year":"2019","journal-title":"Cytotherapy."},{"key":"B10","first-page":"154","article-title":"Biological properties of mesenchymal Stem Cells from different sources","volume":"2","author":"Via","year":"2012","journal-title":"Muscles Ligaments Tendons J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s12929-016-0254-3","article-title":"Mesenchymal stem cells (MSCs) as skeletal therapeutics - an update","volume":"23","author":"Saeed","year":"2016","journal-title":"J Biomed Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"7357213","DOI":"10.1155\/2018\/7357213","article-title":"Induction of expression of CD271 and CD34 in mesenchymal stromal cells cultured as spheroids","volume":"2018","author":"Bellagamba","year":"2018","journal-title":"Stem Cells Int."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.1182\/blood-2005-07-2793","article-title":"Interferon-gamma-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell","volume":"107","author":"Stagg","year":"2006","journal-title":"Blood."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.4049\/jimmunol.179.3.1549","article-title":"Regulation of MHC class II expression and antigen processing in murine and human mesenchymal stromal cells by IFN-gamma, TGF-beta, and cell density","volume":"179","author":"Romieu-Mourez","year":"2007","journal-title":"J Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1146\/annurev-bioeng-070909-105309","article-title":"Mesenchymal stem cells as therapeutics","volume":"12","author":"Parekkadan","year":"2010","journal-title":"Annu Rev Biomed Eng."},{"key":"B16","first-page":"557","article-title":"Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use","volume":"16","author":"Lazarus","year":"1995","journal-title":"Bone Marrow Transplant."},{"key":"B17","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1200\/JCO.2000.18.2.307","article-title":"Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy","volume":"18","author":"Koc","year":"2000","journal-title":"J Clin Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"8932","DOI":"10.1073\/pnas.132252399","article-title":"Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone","volume":"99","author":"Horwitz","year":"2002","journal-title":"Proc Natl Acad Sci USA."},{"key":"B19","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/sj.bmt.1703650","article-title":"Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH)","volume":"30","author":"Koc","year":"2002","journal-title":"Bone Marrow Transplant."},{"key":"B20","doi-asserted-by":"publisher","first-page":"34","DOI":"10.21037\/sci.2019.08.11","article-title":"A revealing review of mesenchymal stem cells therapy, clinical perspectives and modification strategies","volume":"6","author":"Saeedi","year":"2019","journal-title":"Stem Cell Investig."},{"key":"B21","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.stemcr.2016.05.011","article-title":"No identical mesenchymal stem cells at different times and sites: human committed progenitors of distinct origin and differentiation potential are incorporated as adventitial cells in microvessels","volume":"6","author":"Sacchetti","year":"2016","journal-title":"Stem Cell Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1177\/154405910208100806","article-title":"Stem cell properties of human dental pulp stem cells","volume":"81","author":"Gronthos","year":"2002","journal-title":"J Dent Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1002\/jcp.21210","article-title":"Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo","volume":"214","author":"Zannettino","year":"2008","journal-title":"J Cell Physiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"886","DOI":"10.3390\/cells8080886","article-title":"Mesenchymal stem cells for regenerative medicine","volume":"8","author":"Han","year":"2019","journal-title":"Cells."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.1007\/s00018-020-03454-6","article-title":"Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy","volume":"77","author":"Fan","year":"2020","journal-title":"Cell Mol Life Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/8756-3282(92)90364-3","article-title":"Characterization of cells with osteogenic potential from human marrow","volume":"13","author":"Haynesworth","year":"1992","journal-title":"Bone."},{"key":"B27","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science."},{"key":"B28","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s13287-018-0914-1","article-title":"Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison","volume":"9","author":"Mohamed-Ahmed","year":"2018","journal-title":"Stem Cell Res Ther."},{"key":"B29","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1046\/j.1365-2141.2000.01986.x","article-title":"Mesenchymal progenitor cells in human umbilical cord blood","volume":"109","author":"Erices","year":"2000","journal-title":"Br J Haematol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"195","DOI":"10.4252\/wjsc.v6.i2.195","article-title":"Umbilical cord-derived mesenchymal stem cells: their advantages and potential clinical utility","volume":"6","author":"Nagamura-Inoue","year":"2014","journal-title":"World J Stem Cells."},{"key":"B31","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.apjtm.2015.07.022","article-title":"Comparative analysis of biological characteristics of adult mesenchymal stem cells with different tissue origins","volume":"8","author":"Chen","year":"2015","journal-title":"Asian Pac J Trop Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"8429042","DOI":"10.1155\/2018\/8429042","article-title":"Comparison of immunological characteristics of mesenchymal stem cells from the periodontal ligament, umbilical cord, and adipose tissue","volume":"2018","author":"Kim","year":"2018","journal-title":"Stem Cells Int."},{"key":"B33","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.bbrep.2018.10.007","article-title":"Conditioned media from human umbilical cord blood-derived mesenchymal stem cells stimulate rejuvenation function in human skin","volume":"16","author":"Kim","year":"2018","journal-title":"Biochem Biophys Rep."},{"key":"B34","first-page":"1017","article-title":"Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials","volume":"91","author":"Lu","year":"2006","journal-title":"Haematologica."},{"key":"B35","doi-asserted-by":"publisher","first-page":"373","DOI":"10.5507\/bp.2013.078","article-title":"Comparison of human mesenchymal stem cells derived from dental pulp, bone marrow, adipose tissue, and umbilical cord tissue by gene expression","volume":"158","author":"Stanko","year":"2014","journal-title":"Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub."},{"key":"B36","doi-asserted-by":"publisher","first-page":"6376271","DOI":"10.1155\/2019\/6376271","article-title":"Characterization of human mesenchymal stem cells from different tissues and their membrane encasement for prospective transplantation therapies","volume":"2019","author":"Schmelzer","year":"2019","journal-title":"Biomed Res Int."},{"key":"B37","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1089\/107632701300062859","article-title":"Multilineage cells from human adipose tissue: implications for cell-based therapies","volume":"7","author":"Zuk","year":"2001","journal-title":"Tissue Eng."},{"key":"B38","doi-asserted-by":"publisher","first-page":"3932615","DOI":"10.1155\/2018\/3932615","article-title":"Comparative analysis of human adipose-derived mesenchymal stem cells from orbital and abdominal fat","volume":"2018","author":"Nepali","year":"2018","journal-title":"Stem Cells Int."},{"key":"B39","doi-asserted-by":"publisher","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":"De Bari","year":"2001","journal-title":"Arthritis Rheum."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2942","DOI":"10.1177\/0363546518794664","article-title":"Synovial mesenchymal stem cells derived from the cotyloid fossa synovium have higher self-renewal and differentiation potential than those from the paralabral synovium in the hip joint","volume":"46","author":"Murata","year":"2018","journal-title":"Am J Sports Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1186\/s13287-020-01885-3","article-title":"Synovial membrane mesenchymal stem cells: past life, current situation, and application in bone and joint diseases","volume":"11","author":"Li","year":"2020","journal-title":"Stem Cell Res Ther."},{"key":"B42","doi-asserted-by":"publisher","first-page":"174","DOI":"10.2174\/1574888X12666171002111026","article-title":"The potential for synovium-derived stem cells in cartilage repair","volume":"13","author":"Kubosch","year":"2018","journal-title":"Curr Stem Cell Res Ther."},{"key":"B43","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1002\/art.21651","article-title":"Higher chondrogenic potential of fibrous synovium- and adipose synovium-derived cells compared with subcutaneous fat-derived cells: distinguishing properties of mesenchymal stem cells in humans","volume":"54","author":"Mochizuki","year":"2006","journal-title":"Arthritis Rheum."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e0129096","DOI":"10.1371\/journal.pone.0129096","article-title":"Purified human synovium mesenchymal stem cells as a good resource for cartilage regeneration","volume":"10","author":"Ogata","year":"2015","journal-title":"PLoS ONE."},{"key":"B45","doi-asserted-by":"publisher","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 Rheum."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e400","DOI":"10.1111\/sms.12330","article-title":"Trends in arthroscopy-documented cartilage injuries of the knee and repair procedures among 15-60-year-old patients","volume":"25","author":"Mor","year":"2015","journal-title":"Scand J Med Sci Sports."},{"key":"B47","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41536-019-0074-7","article-title":"Emerging therapies for cartilage regeneration in currently excluded 'red knee' populations","volume":"4","author":"Martin","year":"2019","journal-title":"NPJ Regen Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.21873\/invivo.11379","article-title":"Treatment of articular cartilage defects: focus on tissue engineering","volume":"32","author":"Zylinska","year":"2018","journal-title":"In Vivo."},{"key":"B49","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.jot.2019.06.002","article-title":"Current surgical options and innovation for repairing articular cartilage defects in the femoral head","volume":"21","author":"Du","year":"2020","journal-title":"J Orthop Translat."},{"key":"B50","doi-asserted-by":"publisher","first-page":"595","DOI":"10.3727\/000000004783983747","article-title":"Autologous bone marrow stromal cell transplantation for repair of full-thickness articular cartilage defects in human patellae: two case reports","volume":"13","author":"Wakitani","year":"2004","journal-title":"Cell Transplant."},{"key":"B51","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.joca.2006.08.008","article-title":"Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells","volume":"15","author":"Kuroda","year":"2007","journal-title":"Osteoarthritis Cartilage."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1177\/0363546509359067","article-title":"Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study","volume":"38","author":"Nejadnik","year":"2010","journal-title":"Am J Sports Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41413-018-0016-9","article-title":"Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies","volume":"6","author":"Guo","year":"2018","journal-title":"Bone Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"45","DOI":"10.3389\/fmed.2019.00045","article-title":"Synovial tissue heterogeneity in rheumatoid arthritis and changes with biologic and targeted synthetic therapies to inform stratified therapy","volume":"6","author":"Ouboussad","year":"2019","journal-title":"Front Med."},{"key":"B55","doi-asserted-by":"publisher","first-page":"16044","DOI":"10.1038\/boneres.2016.44","article-title":"Osteoarthritis: toward a comprehensive understanding of pathological mechanism","volume":"5","author":"Chen","year":"2017","journal-title":"Bone Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"6093","DOI":"10.3390\/ijms16036093","article-title":"Osteoarthritis in the XXIst century: risk factors and behaviours that influence disease onset and progression","volume":"16","author":"Musumeci","year":"2015","journal-title":"Int J Mol Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1159\/000493390","article-title":"Rheumatoid arthritis: a brief overview of the treatment","volume":"27","author":"Bullock","year":"2018","journal-title":"Med Princ Pract."},{"key":"B58","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.2147\/JPR.S154002","article-title":"Knee osteoarthritis: pathophysiology and current treatment modalities","volume":"11","author":"Mora","year":"2018","journal-title":"J Pain Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"46","DOI":"10.7326\/M14-1231","article-title":"Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis","volume":"162","author":"Bannuru","year":"2015","journal-title":"Ann Intern Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.semarthrit.2013.11.012","article-title":"A systematic review of recommendations and guidelines for the management of osteoarthritis: the chronic osteoarthritis management initiative of the U.S. bone and joint initiative","volume":"43","author":"Nelson","year":"2014","journal-title":"Semin Arthritis Rheum."},{"key":"B61","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1002\/art.21562","article-title":"Projections of US prevalence of arthritis and associated activity limitations","volume":"54","author":"Hootman","year":"2006","journal-title":"Arthritis Rheum."},{"key":"B62","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1136\/ard.2007.073874","article-title":"Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review","volume":"67","author":"Ryder","year":"2008","journal-title":"Ann Rheum Dis."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1177\/0363546512449306","article-title":"A population-based nationwide study of cruciate ligament injury in Sweden, 2001-2009: incidence, treatment, and sex differences","volume":"40","author":"Nordenvall","year":"2012","journal-title":"Am J Sports Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1097\/BOR.0000000000000479","article-title":"Epidemiology of osteoarthritis: literature update","volume":"30","author":"Vina","year":"2018","journal-title":"Curr Opin Rheumatol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1097\/BOR.0b013e32835a9428","article-title":"Aging processes and the development of osteoarthritis","volume":"25","author":"Loeser","year":"2013","journal-title":"Curr Opin Rheumatol."},{"key":"B66","first-page":"44","article-title":"The role of aging in the development of osteoarthritis","volume":"128","author":"Loeser","year":"2017","journal-title":"Trans Am Clin Climatol Assoc."},{"key":"B67","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1097\/BOR.0b013e3283494005","article-title":"Aging and osteoarthritis","volume":"23","author":"Loeser","year":"2011","journal-title":"Curr Opin Rheumatol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1084\/jem.20110367","article-title":"Mitochondrial reactive oxygen species drive proinflammatory cytokine production","volume":"208","author":"Naik","year":"2011","journal-title":"J Exp Med."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1002\/jor.21091","article-title":"Rotenone prevents impact-induced chondrocyte death","volume":"28","author":"Goodwin","year":"2010","journal-title":"J Orthop Res."},{"key":"B70","doi-asserted-by":"publisher","first-page":"12","DOI":"10.15386\/mpr-1422","article-title":"The evaluation of oxidative stress in osteoarthritis","volume":"93","author":"Zahan","year":"2020","journal-title":"Med Pharm Rep."},{"key":"B71","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.berh.2014.01.004","article-title":"The epidemiology of osteoarthritis","volume":"28","author":"Johnson","year":"2014","journal-title":"Best Pract Res Clin Rheumatol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1002\/acr.22897","article-title":"Number of persons with symptomatic knee osteoarthritis in the us: impact of race and ethnicity, age, sex, and obesity","volume":"68","author":"Deshpande","year":"2016","journal-title":"Arthritis Care Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.joca.2019.11.010","article-title":"Osteoarthritis year in review 2019: genetics, genomics and epigenetics","volume":"28","author":"Reynard","year":"2020","journal-title":"Osteoarthritis Cartilage."},{"key":"B74","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/s41588-018-0327-1","article-title":"Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data","volume":"51","author":"Tachmazidou","year":"2019","journal-title":"Nat Genet."},{"key":"B75","doi-asserted-by":"publisher","first-page":"9757","DOI":"10.1073\/pnas.0403456101","article-title":"Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females","volume":"101","author":"Loughlin","year":"2004","journal-title":"Proc Natl Acad Sci USA."},{"key":"B76","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.joca.2013.01.011","article-title":"Association study of candidate genes for the progression of hand osteoarthritis","volume":"21","author":"Bijsterbosch","year":"2013","journal-title":"Osteoarthritis Cartilage."},{"key":"B77","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1002\/art.27530","article-title":"Genetic variation in the SMAD3 gene is associated with hip and knee osteoarthritis","volume":"62","author":"Valdes","year":"2010","journal-title":"Arthritis Rheum."},{"key":"B78","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.joca.2003.12.002","article-title":"A type XI collagen mutation leads to increased degradation of type II collagen in articular cartilage","volume":"12","author":"Rodriguez","year":"2004","journal-title":"Osteoarthritis Cartilage."},{"key":"B79","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1186\/1471-2474-15-371","article-title":"Novel COL9A3 mutation in a family diagnosed with multiple epiphyseal dysplasia: a case report","volume":"15","author":"Jeong","year":"2014","journal-title":"BMC Musculoskelet Disord."},{"key":"B80","first-page":"1133","article-title":"Precocious osteoarthritis in a family with recurrent COL2A1 mutation","volume":"33","author":"Carlson","year":"2006","journal-title":"J Rheumatol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s00011-015-0818-9","article-title":"A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand","volume":"64","author":"Zhang","year":"2015","journal-title":"Inflamm Res."},{"key":"B82","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/ng.3816","article-title":"Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis","volume":"49","author":"Styrkarsdottir","year":"2017","journal-title":"Nat Genet."},{"key":"B83","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/s41588-018-0079-y","article-title":"Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis","volume":"50","author":"Zengini","year":"2018","journal-title":"Nat Genet."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1038\/s41588-018-0247-0","article-title":"Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis","volume":"50","author":"Styrkarsdottir","year":"2018","journal-title":"Nat Genet."},{"key":"B85","doi-asserted-by":"publisher","first-page":"2358","DOI":"10.1038\/s41467-019-10425-4","article-title":"Publisher Correction: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures","volume":"10","author":"Styrkarsdottir","year":"2019","journal-title":"Nat Commun."},{"key":"B86","doi-asserted-by":"publisher","first-page":"BSR20192999","DOI":"10.1042\/BSR20192999","article-title":"Common variants in LTBP3 gene contributed to the risk of hip osteoarthritis in Han Chinese population","volume":"40","author":"Zhao","year":"2020","journal-title":"Biosci Rep."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/j.joca.2017.01.003","article-title":"The rs4238326 polymorphism in ALDH1A2 gene potentially associated with non-post traumatic knee osteoarthritis susceptibility: a two-stage population-based study","volume":"25","author":"Chu","year":"2017","journal-title":"Osteoarthritis Cartilage."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1038\/ijo.2008.102","article-title":"Global burden of obesity in 2005 and projections to 2030","volume":"32","author":"Kelly","year":"2008","journal-title":"Int J Obes"},{"key":"B89","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/s13075-015-0601-x","article-title":"Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis","volume":"17","author":"Qin","year":"2015","journal-title":"Arthritis Res Ther."},{"key":"B90","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/j.joca.2015.01.013","article-title":"Diabetes is a risk factor for knee osteoarthritis progression","volume":"23","author":"Eymard","year":"2015","journal-title":"Osteoarthritis Cartilage."},{"key":"B91","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.1038\/s41598-020-60989-1","article-title":"The association of diabetes with knee pain severity and distribution in people with knee osteoarthritis using data from the osteoarthritis initiative","volume":"10","author":"Alenazi","year":"2020","journal-title":"Sci Rep."},{"key":"B92","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s11926-019-0868-z","article-title":"Adipokines: new therapeutic target for osteoarthritis?","volume":"21","author":"Xie","year":"2019","journal-title":"Curr Rheumatol Rep."},{"key":"B93","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.joca.2012.11.012","article-title":"Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)","volume":"21","author":"Berenbaum","year":"2013","journal-title":"Osteoarthritis Cartilage"},{"key":"B94","doi-asserted-by":"publisher","first-page":"203901","DOI":"10.1155\/2011\/203901","article-title":"Adipokines and osteoarthritis: novel molecules involved in the pathogenesis and progression of disease","volume":"2011","author":"Conde","year":"2011","journal-title":"Arthritis."},{"key":"B95","doi-asserted-by":"publisher","first-page":"513948","DOI":"10.1155\/2010\/513948","article-title":"Release of inflammatory mediators by human adipose tissue is enhanced in obesity and primarily by the nonfat cells: a review","volume":"2010","author":"Fain","year":"2010","journal-title":"Mediators Inflamm."},{"key":"B96","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/s0899-9007(01)00509-3","article-title":"Higher levels of inflammation in obese children","volume":"17","author":"Visser","year":"2001","journal-title":"Nutrition."},{"key":"B97","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1155\/MI.2005.180","article-title":"Proinflammatory cytokines and leptin are increased in serum of prepubertal obese children","volume":"2005","author":"Aygun","year":"2005","journal-title":"Mediators Inflamm."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1161\/CIRCULATIONAHA.107.710509","article-title":"Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the Framingham Heart Study","volume":"116","author":"Pou","year":"2007","journal-title":"Circulation."},{"key":"B99","doi-asserted-by":"publisher","first-page":"4602","DOI":"10.1210\/jc.2002-020135","article-title":"Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system","volume":"87","author":"Straczkowski","year":"2002","journal-title":"J Clin Endocrinol Metab."},{"key":"B100","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1089\/jir.2013.0078","article-title":"IL-6 and TNF-alpha induced obesity-related inflammatory response through transcriptional regulation of miR-146b","volume":"34","author":"Shi","year":"2014","journal-title":"J Interferon Cytokine Res."},{"key":"B101","doi-asserted-by":"publisher","first-page":"139239","DOI":"10.1155\/2013\/139239","article-title":"Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines","volume":"2013","author":"Makki","year":"2013","journal-title":"ISRN Inflamm."},{"key":"B102","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1007\/s00011-015-0872-3","article-title":"Sam68 promotes NF-kappaB activation and apoptosis signaling in articular chondrocytes during osteoarthritis","volume":"64","author":"Xu","year":"2015","journal-title":"Inflamm Res."},{"key":"B103","doi-asserted-by":"publisher","first-page":"8293921","DOI":"10.1155\/2020\/8293921","article-title":"The role of inflammation in the pathogenesis of osteoarthritis","volume":"2020","author":"Chow","year":"2020","journal-title":"Mediators Inflamm."},{"key":"B104","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nrrheum.2010.196","article-title":"Role of proinflammatory cytokines in the pathophysiology of osteoarthritis","volume":"7","author":"Kapoor","year":"2011","journal-title":"Nat Rev Rheumatol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.jbspin.2011.05.015","article-title":"Body mass index and susceptibility to knee osteoarthritis: a systematic review and meta-analysis","volume":"79","author":"Jiang","year":"2012","journal-title":"Joint Bone Spine."},{"key":"B106","doi-asserted-by":"publisher","first-page":"3601","DOI":"10.1038\/s41598-020-60587-1","article-title":"Level of obesity is directly associated with the clinical and functional consequences of knee osteoarthritis","volume":"10","author":"Raud","year":"2020","journal-title":"Sci Rep."},{"key":"B107","doi-asserted-by":"publisher","first-page":"e204049","DOI":"10.1001\/jamanetworkopen.2020.4049","article-title":"Association of long-term strenuous physical activity and extensive sitting with incident radiographic knee osteoarthritis","volume":"3","author":"Chang","year":"2020","journal-title":"JAMA Netw Open."},{"key":"B108","doi-asserted-by":"publisher","first-page":"e12103","DOI":"10.1002\/1348-9585.12103","article-title":"Risk factors for development of lower limb osteoarthritis in physically demanding occupations: a narrative umbrella review","volume":"62","author":"Schram","year":"2020","journal-title":"J Occup Health."},{"key":"B109","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1002\/acr.23855","article-title":"Men and women's occupational activities and the risk of developing osteoarthritis of the knee, hip, or hands: a systematic review and recommendations for future research","volume":"72","author":"Gignac","year":"2020","journal-title":"Arthritis Care Res."},{"key":"B110","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/1471-2474-10-93","article-title":"The Intensive Diet and Exercise for Arthritis (IDEA) trial: design and rationale","volume":"10","author":"Messier","year":"2009","journal-title":"BMC Musculoskelet Disord"},{"key":"B111","doi-asserted-by":"publisher","first-page":"373","DOI":"10.2519\/jospt.2017.7137","article-title":"The association of recreational and competitive running with hip and knee osteoarthritis: a systematic review and meta-analysis","volume":"47","author":"Alentorn-Geli","year":"2017","journal-title":"J Orthop Sports Phys Ther."},{"key":"B112","doi-asserted-by":"publisher","first-page":"497","DOI":"10.4085\/1062-6050-50.2.08","article-title":"Is participation in certain sports associated with knee osteoarthritis? A systematic review","volume":"52","author":"Driban","year":"2017","journal-title":"J Athl Train."},{"key":"B113","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.1007\/s40279-020-01310-y","article-title":"Cumulative sport-related injuries and longer term impact in retired male elite- and amateur-level rugby code athletes and non-contact athletes: a retrospective study","volume":"50","author":"Hind","year":"2020","journal-title":"Sports Med."},{"key":"B114","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s12891-020-3136-5","article-title":"Playing sport injured is associated with osteoarthritis, joint pain and worse health-related quality of life: a cross-sectional study","volume":"21","author":"Bullock","year":"2020","journal-title":"BMC Musculoskelet Disord."},{"key":"B115","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1177\/0363546515588317","article-title":"Mesenchymal stem cell implantation in knee osteoarthritis: an assessment of the factors influencing clinical outcomes","volume":"43","author":"Kim","year":"2015","journal-title":"Am J Sports Med."},{"key":"B116","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1177\/0363546516662455","article-title":"A prospective, single-blind, placebo-controlled trial of bone marrow aspirate concentrate for knee osteoarthritis","volume":"45","author":"Shapiro","year":"2017","journal-title":"Am J Sports Med."},{"key":"B117","doi-asserted-by":"publisher","first-page":"847","DOI":"10.5966\/sctm.2015-0245","article-title":"Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase i dose-escalation trial","volume":"5","author":"Pers","year":"2016","journal-title":"Stem Cells Transl Med."},{"key":"B118","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1002\/sctm.18-0053","article-title":"Umbilical cord-derived Mesenchymal Stromal Cells (MSCs) for knee osteoarthritis: repeated msc dosing is superior to a single MSC dose and to hyaluronic acid in a controlled randomized phase I\/II trial","volume":"8","author":"Matas","year":"2019","journal-title":"Stem Cells Transl Med"},{"key":"B119","doi-asserted-by":"publisher","first-page":"213","DOI":"10.2217\/rme-2018-0161","article-title":"Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial","volume":"14","author":"Freitag","year":"2019","journal-title":"Regen Med."},{"key":"B120","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1002\/sctm.18-0183","article-title":"Bone marrow mesenchymal stromal cell treatment in patients with osteoarthritis results in overall improvement in pain and symptoms and reduces synovial inflammation","volume":"8","author":"Chahal","year":"2019","journal-title":"Stem Cells Transl Med."},{"key":"B121","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/sctm.18-0122","article-title":"Intra-articular injection of autologous adipose tissue-derived mesenchymal stem cells for the treatment of knee osteoarthritis: a phase IIb, randomized, placebo-controlled clinical trial","volume":"8","author":"Lee","year":"2019","journal-title":"Stem Cells Transl Med."},{"key":"B122","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.3346\/jkms.2017.32.7.1207","article-title":"A case of rheumatoid vasculitis involving hepatic artery in early rheumatoid arthritis","volume":"32","author":"Lee","year":"2017","journal-title":"J Korean Med Sci."},{"key":"B123","doi-asserted-by":"publisher","first-page":"S265","DOI":"10.1186\/ar578","article-title":"Epidemiology and genetics of rheumatoid arthritis","volume":"4","author":"Silman","year":"2002","journal-title":"Arthritis Res."},{"key":"B124","doi-asserted-by":"publisher","first-page":"983","DOI":"10.3899\/jrheum.101133","article-title":"Incidence of extraarticular rheumatoid arthritis in Olmsted County, Minnesota, in 1995-2007 versus 1985-1994: a population-based study","volume":"38","author":"Myasoedova","year":"2011","journal-title":"J Rheumatol."},{"key":"B125","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/nrrheum.2011.28","article-title":"Rheumatoid arthritis: are ACPA-positive and ACPA-negative RA the same disease?","volume":"7","author":"Daha","year":"2011","journal-title":"Nat Rev Rheumatol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"6916","DOI":"10.1093\/hmg\/ddu387","article-title":"Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations","volume":"23","author":"Okada","year":"2014","journal-title":"Hum Mol Genet."},{"key":"B127","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/ng.1076","article-title":"Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis","volume":"44","author":"Raychaudhuri","year":"2012","journal-title":"Nat Genet."},{"key":"B128","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.berh.2017.08.003","article-title":"Genetic and environmental risk factors for rheumatoid arthritis","volume":"31","author":"Deane","year":"2017","journal-title":"Best Pract Res Clin Rheumatol."},{"key":"B129","doi-asserted-by":"publisher","first-page":"R79","DOI":"10.1186\/4ar1949","article-title":"Validation of the reshaped shared epitope HLA-DRB1 classification in rheumatoid arthritis.","volume":"8","author":"Michou","year":"2006","journal-title":"Arthritis Res Ther."},{"key":"B130","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1002\/art.20989","article-title":"New classification of HLA-DRB1 alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility.","volume":"52","author":"du Mellado","year":"2005","journal-title":"Arthritis Rheum."},{"key":"B131","doi-asserted-by":"publisher","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":"B132","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1111\/imr.12829","article-title":"Autoantibodies and B Cells: the ABC of rheumatoid arthritis pathophysiology","volume":"294","author":"Volkov","year":"2020","journal-title":"Immunol Rev."},{"key":"B133","doi-asserted-by":"publisher","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":"B134","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3904\/kjim.1999.14.1.59","article-title":"Expression of p53 protein in rheumatoid arthritis synovium. An immunohistochemical analysis","volume":"14","author":"Lee","year":"1999","journal-title":"Korean J Intern Med."},{"key":"B135","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/nrrheum.2015.95","article-title":"Cartilage damage in osteoarthritis and rheumatoid arthritis\u2013two unequal siblings","volume":"11","author":"Pap","year":"2015","journal-title":"Nat Rev Rheumatol."},{"key":"B136","doi-asserted-by":"publisher","first-page":"8526","DOI":"10.1038\/s41598-019-44747-6","article-title":"Detection of fine radiographic progression in finger joint space narrowing beyond human eyes: phantom experiment and clinical study with rheumatoid arthritis patients","volume":"9","author":"Kato","year":"2019","journal-title":"Sci Rep."},{"key":"B137","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1093\/qjmed\/hcu033","article-title":"Mesenchymal stem cells, autoimmunity and rheumatoid arthritis","volume":"107","author":"El-Jawhari","year":"2014","journal-title":"QJM."},{"key":"B138","doi-asserted-by":"publisher","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":"B139","doi-asserted-by":"publisher","first-page":"e7023","DOI":"10.7717\/peerj.7023","article-title":"Comparison of therapeutic effects of different mesenchymal stem cells on rheumatoid arthritis in mice","volume":"7","author":"Zhang","year":"2019","journal-title":"PeerJ."},{"key":"B140","doi-asserted-by":"publisher","first-page":"3192","DOI":"10.1089\/scd.2013.0023","article-title":"Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy","volume":"22","author":"Wang","year":"2013","journal-title":"Stem Cells Dev."},{"key":"B141","doi-asserted-by":"publisher","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":"B142","doi-asserted-by":"publisher","first-page":"3562753","DOI":"10.1155\/2020\/3562753","article-title":"The sufficient immunoregulatory effect of autologous bone marrow-derived mesenchymal stem cell transplantation on regulatory T cells in patients with refractory rheumatoid arthritis","volume":"2020","author":"Ghoryani","year":"2020","journal-title":"J Immunol Res."},{"key":"B143","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1080\/14653240500319234","article-title":"Clarification of the nomenclature for MSC: the international society for cellular therapy position statement","volume":"7","author":"Horwitz","year":"2005","journal-title":"Cytotherapy."},{"key":"B144","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.cell.2007.08.025","article-title":"Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment","volume":"131","author":"Sacchetti","year":"2007","journal-title":"Cell."},{"key":"B145","doi-asserted-by":"publisher","first-page":"43","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":"B146","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nri3209","article-title":"Multipotent mesenchymal stromal cells and the innate immune system","volume":"12","author":"Le Blanc","year":"2012","journal-title":"Nat Rev Immunol."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.631291\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T05:56:03Z","timestamp":1615182963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.631291\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,8]]},"references-count":146,"alternative-id":["10.3389\/fimmu.2021.631291"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.631291","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,8]]},"article-number":"631291"}}