{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:26:34Z","timestamp":1787567194482,"version":"build-2736575974"},"reference-count":81,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["T32 EB001026"],"award-info":[{"award-number":["T32 EB001026"]}]},{"award":["T32 EB001026"],"award-info":[{"award-number":["T32 EB001026"]}],"id":[{"id":"https:\/\/ror.org\/05h1kgg64","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Cellular Approaches to Tissue Engineering and Regeneration, Cardiovascular Bioengineering Training Program","award":["T32- HL076124"],"award-info":[{"award-number":["T32- HL076124"]}]},{"name":"Ruth L Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship","award":["1F31AR083814 \u2013 01A1"],"award-info":[{"award-number":["1F31AR083814 \u2013 01A1"]}]},{"name":"University of Pittsburgh School of Medicine","award":["Department of Orthopaedic Surgery Startup Fund"],"award-info":[{"award-number":["Department of Orthopaedic Surgery Startup Fund"]}]},{"award":["Department of Orthopaedic Surgery Startup Fund"],"award-info":[{"award-number":["Department of Orthopaedic Surgery Startup Fund"]}],"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of Pittsburgh School of Medicine","award":["Orland Bethel Family Musculoskeletal Research Center (BMRC)"],"award-info":[{"award-number":["Orland Bethel Family Musculoskeletal Research Center (BMRC)"]}]},{"award":["Orland Bethel Family Musculoskeletal Research Center (BMRC)"],"award-info":[{"award-number":["Orland Bethel Family Musculoskeletal Research Center (BMRC)"]}],"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Although the causal association between aging and osteoarthritis (OA) has been documented, our understanding of the underlying mechanism remains incomplete. To define the regulatory molecules governing chondrocyte aging, we performed transcriptomic analysis of young and old human chondrocytes from healthy donors. The data predicted that GATA-binding protein 4 (GATA4) may play a key role in mediating the difference between young and old chondrocytes. Results from immunostaining and western blot showed significantly higher GATA4 levels in old human or mouse chondrocytes when compared to young cells. Moreover, overexpressing\n                    <jats:italic>GATA4<\/jats:italic>\n                    in young chondrocytes remarkably reduced their cartilage-forming capacity in vitro and induced the upregulation of proinflammatory cytokines. Conversely, suppressing\n                    <jats:italic>GATA4<\/jats:italic>\n                    expression in old chondrocytes, through either siRNA or a small-molecule inhibitor NSC140905, increased the production of aggrecan and collagen type II, and also decreased levels of matrix-degrading enzymes. In OA mice induced by surgical destabilization of the medial meniscus, intra-articular injection of lentiviral vectors carrying mouse\n                    <jats:italic>Gata4<\/jats:italic>\n                    resulted in a higher OA severity, synovial inflammation, and pain level when compared to control vectors. Mechanistically, we found that overexpressing GATA4 significantly increased the phosphorylation of SMAD1\/5. Our work demonstrates that the aging-associated increase of GATA4 in chondrocytes plays a vital role in OA progression, which may also serve as a target to reduce OA in the older population.\n                  <\/jats:p>","DOI":"10.7554\/elife.106224","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T10:30:13Z","timestamp":1748514613000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.106224","source":"Crossref","is-referenced-by-count":0,"title":["Aging-associated increase of GATA4 levels in articular cartilage is linked to impaired regenerative capacity of chondrocytes and osteoarthritis"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3444-8028","authenticated-orcid":true,"given":"Meagan J","family":"Makarczyk","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine","place":["Pittsburgh, United States"]},{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Bioengineering, University of Pittsburgh Swanson School of Engineering","place":["Pittsburgh, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yiqian","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine","place":["Pittsburgh, United States"]},{"id":[{"id":"https:\/\/ror.org\/05c1yfj14","id-type":"ROR","asserted-by":"publisher"}],"name":"Xiangya Hospital Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Alyssa","family":"Aguglia","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Bioengineering, University of Pittsburgh Swanson School of Engineering","place":["Pittsburgh, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Olivia","family":"Bartholomew","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Bioengineering, University of Pittsburgh Swanson School of Engineering","place":["Pittsburgh, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Sophie","family":"Hines","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine","place":["Pittsburgh, United States"]},{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Bioengineering, University of Pittsburgh Swanson School of Engineering","place":["Pittsburgh, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Kate","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Sciences, University of Pittsburgh Kenneth P. Dietrich School of Arts & Sciences","place":["Pittsburgh, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Suyash","family":"Sinkar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Bioengineering, University of Pittsburgh Swanson School of Engineering","place":["Pittsburgh, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Silvia","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine","place":["Pittsburgh, United States"]},{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Organ Pathobiology and Therapeutics Institute, University of Pittsburgh School of Medicine","place":["Pittsburgh, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Craig","family":"Duvall","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Engineering, Vanderbilt University","place":["Nashville, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0781-6630","authenticated-orcid":true,"given":"Hang","family":"Lin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine","place":["Pittsburgh, United States"]},{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Bioengineering, University of Pittsburgh Swanson School of Engineering","place":["Pittsburgh, United States"]},{"id":[{"id":"https:\/\/ror.org\/01an3r305","id-type":"ROR","asserted-by":"publisher"}],"name":"Bethel Family Musculoskeletal Research Center (BMRC), University of Pittsburgh School of Medicine","place":["Pittsburgh, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"3244","DOI":"10.1101\/gad.1588507","type":"journal-article","article-title":"Motif module map reveals enforcement of aging by continual NF-kappaB activity","volume":"21","author":"Adler","year":"2007","journal-title":"Genes & Development"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"3731","DOI":"10.1091\/mbc.E12-03-0172","type":"journal-article","article-title":"ECM stiffness primes the TGF\u03b2 pathway to promote chondrocyte differentiation","volume":"23","author":"Allen","year":"2012","journal-title":"Molecular Biology of the Cell"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1016\/j.cell.2016.11.033","type":"journal-article","article-title":"Disease model of GATA4 mutation reveals transcription factor cooperativity in human cardiogenesis","volume":"167","author":"Ang","year":"2016","journal-title":"Cell"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.joca.2004.02.010","type":"journal-article","article-title":"Age related changes in human articular chondrocyte yield, proliferation and post-expansion chondrogenic capacity","volume":"12","author":"Barbero","year":"2004","journal-title":"Osteoarthritis and Cartilage"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jneumeth.2007.02.012","type":"journal-article","article-title":"Pressure application measurement (PAM): a novel behavioural technique for measuring hypersensitivity in a rat model of joint pain","volume":"163","author":"Barton","year":"2007","journal-title":"Journal of Neuroscience Methods"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"394","DOI":"10.14336\/AD.2014.0500394","type":"journal-article","article-title":"Regulation and role of TGF\u03b2 signaling pathway in aging and osteoarthritis joints","volume":"5","author":"Baug\u00e9","year":"2014","journal-title":"Aging and Disease"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.44","type":"journal-article","article-title":"Osteoarthritis: toward a comprehensive understanding of pathological mechanism","volume":"5","author":"Chen","year":"2017","journal-title":"Bone Research"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1136\/annrheumdis-2021-221091","type":"journal-article","article-title":"METTL3-mediated m6A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression","volume":"81","author":"Chen","year":"2022","journal-title":"Annals of the Rheumatic Diseases"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.matbio.2020.11.002","type":"journal-article","article-title":"Decorin regulates cartilage pericellular matrix micromechanobiology","volume":"96","author":"Chery","year":"2021","journal-title":"Matrix Biology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/ijos.2016.57","type":"journal-article","article-title":"Distribution of pericellular matrix molecules in the temporomandibular joint and their chondroprotective effects against inflammation","volume":"9","author":"Chu","year":"2017","journal-title":"International Journal of Oral Science"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s00204-019-02607-2","type":"journal-article","article-title":"Arsenic induces human chondrocyte senescence and accelerates rat articular cartilage aging","volume":"94","author":"Chung","year":"2020","journal-title":"Archives of Toxicology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1007\/s00204-022-03407-x","type":"journal-article","article-title":"Low-dose tributyltin triggers human chondrocyte senescence and mouse articular cartilage aging","volume":"97","author":"Chung","year":"2023","journal-title":"Archives of Toxicology"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13698","type":"journal-article","article-title":"Comet assay for quantification of the increased DNA damage burden in primary human chondrocytes with aging and osteoarthritis","volume":"21","author":"Copp","year":"2022","journal-title":"Aging Cell"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/iub.2178","type":"journal-article","article-title":"The roles and controls of GATA factors in blood and cardiac development","volume":"72","author":"Dobrzycki","year":"2020","journal-title":"IUBMB Life"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2022.111336","type":"journal-article","article-title":"Impacts of aging on murine cartilage biomechanics and chondrocyte in situ calcium signaling","volume":"144","author":"Fan","year":"2022","journal-title":"Journal of Biomechanics"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1093\/gerona\/60.9.1118","type":"journal-article","article-title":"Increased matrix metalloproteinase-13 production with aging by human articular chondrocytes in response to catabolic stimuli","volume":"60","author":"Forsyth","year":"2005","journal-title":"The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","type":"journal-article","article-title":"Inflamm-aging. An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Annals of the New York Academy of Sciences"},{"key":"bib18","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-024-00333-9","type":"journal-article","article-title":"Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3","volume":"12","author":"Fu","year":"2024","journal-title":"Bone Research"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.joca.2007.03.006","type":"journal-article","article-title":"The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129\/SvEv mouse","volume":"15","author":"Glasson","year":"2007","journal-title":"Osteoarthritis and Cartilage"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"199","DOI":"10.2217\/ijr.10.3","type":"journal-article","article-title":"Joint aging and chondrocyte cell death","volume":"5","author":"Grogan","year":"2010","journal-title":"International Journal of Clinical Rheumatology"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.1002\/jbmr.2296","type":"journal-article","article-title":"GATA4 is essential for bone mineralization via ER\u03b1 and TGF\u03b2\/BMP pathways","volume":"29","author":"G\u00fcemes","year":"2014","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.cger.2021.11.005","type":"journal-article","article-title":"The burden of osteoarthritis in older adults","volume":"38","author":"Hawker","year":"2022","journal-title":"Clinics in Geriatric Medicine"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1136\/annrheumdis-2020-219247","type":"journal-article","article-title":"\u201cSMASH\u201d recommendations for standardised microscopic arthritis scoring of histological sections from inflammatory arthritis animal models","volume":"80","author":"Hayer","year":"2021","journal-title":"Annals of the Rheumatic Diseases"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2680-0","type":"journal-article","article-title":"Stabilization of HIF-1\u03b1 alleviates osteoarthritis via enhancing mitophagy","volume":"11","author":"Hu","year":"2020","journal-title":"Cell Death & Disease"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35359-2","type":"journal-article","article-title":"Age-related matrix stiffening epigenetically regulates \u03b1-Klotho expression and compromises chondrocyte integrity","volume":"14","author":"Iijima","year":"2023","journal-title":"Nature Communications"},{"key":"bib26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35424-w","type":"journal-article","article-title":"Sirt6 attenuates chondrocyte senescence and osteoarthritis progression","volume":"13","author":"Ji","year":"2022","journal-title":"Nature Communications"},{"key":"bib27","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0570-5","type":"journal-article","article-title":"GATA4 regulates angiogenesis and persistence of inflammation in rheumatoid arthritis","volume":"9","author":"Jia","year":"2018","journal-title":"Cell Death & Disease"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1002\/stem.3297","type":"journal-article","article-title":"GATA6 regulates aging of human mesenchymal stem\/stromal cells","volume":"39","author":"Jiao","year":"2021","journal-title":"Stem Cells"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa5612","type":"journal-article","article-title":"The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4","volume":"349","author":"Kang","year":"2015","journal-title":"Science"},{"key":"bib30","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar6659","type":"journal-article","article-title":"Stress-activated miR-204 governs senescent phenotypes of chondrocytes to promote osteoarthritis development","volume":"11","author":"Kang","year":"2019","journal-title":"Science Translational Medicine"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1536\/ihj.16-404","type":"journal-article","article-title":"Regulation of cardiac transcription factor GATA4 by post-translational modification in cardiomyocyte hypertrophy and heart failure","volume":"57","author":"Katanasaka","year":"2016","journal-title":"International Heart Journal"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1136\/ard.41.5.508","type":"journal-article","article-title":"Relationship between the tensile properties of articular cartilage from the human knee and age","volume":"41","author":"Kempson","year":"1982","journal-title":"Annals of the Rheumatic Diseases"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"39401","DOI":"10.1074\/jbc.M110.103705","type":"journal-article","article-title":"Induction of interleukin-6 expression by bone morphogenetic protein-6 in macrophages requires both SMAD and p38 signaling pathways","volume":"285","author":"Lee","year":"2010","journal-title":"The Journal of Biological Chemistry"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.jsb.2012.12.008","type":"journal-article","article-title":"Age-related nanostructural and nanomechanical changes of individual human cartilage aggrecan monomers and their glycosaminoglycan side chains","volume":"181","author":"Lee","year":"2013","journal-title":"Journal of Structural Biology"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1358\/mf.2010.32.8.1532102","type":"journal-article","article-title":"Validation of the digital pressure application measurement (PAM) device for detection of primary mechanical hyperalgesia in rat and mouse antigen-induced knee joint arthritis","volume":"32","author":"Leuchtweis","year":"2010","journal-title":"Methods and Findings in Experimental and Clinical Pharmacology"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1002\/art.41254","type":"journal-article","article-title":"Mediation of cartilage matrix degeneration and fibrillation by decorin in post\u2010traumatic osteoarthritis","volume":"72","author":"Li","year":"2020","journal-title":"Arthritis & Rheumatology"},{"key":"bib37","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202105909","type":"journal-article","article-title":"Human mesenchymal stem cell\u2010derived miniature joint system for disease modeling and drug testing","volume":"9","author":"Li","year":"2022","journal-title":"Advanced Science"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/nrrheum.2016.65","type":"journal-article","article-title":"Ageing and the pathogenesis of osteoarthritis","volume":"12","author":"Loeser","year":"2016","journal-title":"Nature Reviews. Rheumatology"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s10557-019-06863-3","type":"journal-article","article-title":"GATA4-Twist1 signalling in disturbed flow-induced atherosclerosis","volume":"33","author":"Mahmoud","year":"2019","journal-title":"Cardiovascular Drugs and Therapy"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1089\/ten.TEC.2020.0309","type":"journal-article","article-title":"Current models for development of disease-modifying osteoarthritis drugs","volume":"27","author":"Makarczyk","year":"2021","journal-title":"Tissue Engineering. Part C, Methods"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.1080\/15476278.2023.2278235","type":"journal-article","article-title":"Cell therapy approaches for articular cartilage regeneration","volume":"19","author":"Makarczyk","year":"2023","journal-title":"Organogenesis"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012716","type":"journal-article","article-title":"DNA damage sensing by the ATM and ATR kinases","volume":"5","author":"Mar\u00e9chal","year":"2013","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/nrm3434","type":"journal-article","article-title":"TGF\u03b2 signalling in context","volume":"13","author":"Massagu\u00e9","year":"2012","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib44","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-020-0376-x","type":"journal-article","article-title":"ATM, ATR and DNA-PKcs kinases-the lessons from the mouse models: inhibition not equal deletion","volume":"10","author":"Menolfi","year":"2020","journal-title":"Cell & Bioscience"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.jot.2022.02.001","type":"journal-article","article-title":"Targeting the GLP-1\/GLP-1R axis to treat osteoarthritis: a new opportunity?","volume":"32","author":"Meurot","year":"2022","journal-title":"Journal of Orthopaedic Translation"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"38949","DOI":"10.1074\/jbc.R000029200","type":"journal-article","article-title":"The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression","volume":"275","author":"Molkentin","year":"2000","journal-title":"The Journal of Biological Chemistry"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"E478","DOI":"10.1152\/ajpendo.00457.2010","type":"journal-article","article-title":"Loss of intestinal GATA4 prevents diet-induced obesity and promotes insulin sensitivity in mice","volume":"300","author":"Patankar","year":"2011","journal-title":"American Journal of Physiology. Endocrinology and Metabolism"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.jhep.2012.06.028","type":"journal-article","article-title":"Intestinal GATA4 deficiency protects from diet-induced hepatic steatosis","volume":"57","author":"Patankar","year":"2012","journal-title":"Journal of Hepatology"},{"key":"bib49","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24258-6","type":"journal-article","article-title":"The effect of ageing and osteoarthritis on the mechanical properties of cartilage and bone in the human knee joint","volume":"8","author":"Peters","year":"2018","journal-title":"Scientific Reports"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/jor.1100130105","type":"journal-article","article-title":"Lysyl oxidase and Maillard reaction-mediated crosslinks in aging and osteoarthritic rabbit cartilage","volume":"13","author":"Pokharna","year":"1995","journal-title":"Journal of Orthopaedic Research"},{"key":"bib51","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116663","type":"journal-article","article-title":"H2AX: A key player in DNA damage response and a promising target for cancer therapy","volume":"175","author":"Prabhu","year":"2024","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1111\/iej.13180","type":"journal-article","article-title":"Lipopolysaccharide-induced DNA damage response activates nuclear factor \u03baB signalling pathway via GATA4 in dental pulp cells","volume":"52","author":"Qiao","year":"2019","journal-title":"International Endodontic Journal"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"15182","DOI":"10.1073\/pnas.1922072117","type":"journal-article","article-title":"Uncoupling DNA damage from chromatin damage to detoxify doxorubicin","volume":"117","author":"Qiao","year":"2020","journal-title":"PNAS"},{"key":"bib54","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111682","type":"journal-article","article-title":"Double knockin mice show NF-\u03baB trajectories in immune signaling and aging","volume":"41","author":"Rahman","year":"2022","journal-title":"Cell Reports"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.arr.2017.07.004","type":"journal-article","article-title":"Aging and osteoarthritis: Central role of the extracellular matrix","volume":"40","author":"Rahmati","year":"2017","journal-title":"Ageing Research Reviews"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1016\/j.joca.2007.04.011","type":"journal-article","article-title":"Modulation of TGF-\u03b2 signaling by proinflammatory cytokines in articular chondrocytes","volume":"15","author":"Roman-Blas","year":"2007","journal-title":"Osteoarthritis and Cartilage"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/iub.2169","type":"journal-article","article-title":"GATA factor transcriptional activity: Insights from genome-wide binding profiles","volume":"72","author":"Romano","year":"2020","journal-title":"IUBMB Life"},{"key":"bib58","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13773","type":"journal-article","article-title":"STAT3 promotes a youthful epigenetic state in articular chondrocytes","volume":"22","author":"Sarkar","year":"2023","journal-title":"Aging Cell"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00616-5","type":"journal-article","article-title":"NF-\u03baB is a critical mediator of post-mitotic senescence in oligodendrocytes and subsequent white matter loss","volume":"18","author":"Schlett","year":"2023","journal-title":"Molecular Neurodegeneration"},{"key":"bib60","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2014.2","type":"journal-article","article-title":"TGF-\u03b2 signaling and the development of osteoarthritis","volume":"2","author":"Shen","year":"2014","journal-title":"Bone Research"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002386R","type":"journal-article","article-title":"Enhancing the potential of aged human articular chondrocytes for high-quality cartilage regeneration","volume":"35","author":"Shen","year":"2021","journal-title":"FASEB Journal"},{"key":"bib62","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.607585","type":"journal-article","article-title":"METTL3 promotes activation and inflammation of FLSs through the NF-\u03baB signaling pathway in rheumatoid arthritis","volume":"8","author":"Shi","year":"2021","journal-title":"Frontiers in Medicine"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1016\/j.joca.2023.08.004","type":"journal-article","article-title":"Separating friend from foe: Inhibition of TGF-\u03b2-induced detrimental SMAD1\/5\/9 phosphorylation while maintaining protective SMAD2\/3 signaling in OA chondrocytes","volume":"31","author":"Thielen","year":"2023","journal-title":"Osteoarthritis and Cartilage"},{"key":"bib64","doi-asserted-by":"publisher","DOI":"10.1242\/dev.164384","type":"journal-article","article-title":"GATA transcription factors in development and disease","volume":"145","author":"Tremblay","year":"2018","journal-title":"Development"},{"key":"bib65","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1302-4","type":"journal-article","article-title":"TGF\u03b21-induced SMAD2\/3 and SMAD1\/5 phosphorylation are both ALK5-kinase-dependent in primary chondrocytes and mediated by TAK1 kinase activity","volume":"19","author":"van Caam","year":"2017","journal-title":"Arthritis Research & Therapy"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s00441-011-1194-6","type":"journal-article","article-title":"Age-dependent alteration of TGF-\u03b2 signalling in osteoarthritis","volume":"347","author":"van der Kraan","year":"2012","journal-title":"Cell and Tissue Research"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nrrheum.2016.219","type":"journal-article","article-title":"The changing role of TGF\u03b2 in healthy, ageing and osteoarthritic joints","volume":"13","author":"van der Kraan","year":"2017","journal-title":"Nature Reviews. Rheumatology"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1002\/iub.2170","type":"journal-article","article-title":"GATA factors in pancreas development and disease","volume":"72","author":"Villamayor","year":"2020","journal-title":"IUBMB Life"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.coph.2013.01.010","type":"journal-article","article-title":"Targeting mechanotransduction pathways in osteoarthritis: a focus on the pericellular matrix","volume":"13","author":"Vincent","year":"2013","journal-title":"Current Opinion in Pharmacology"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1002\/path.5774","type":"journal-article","article-title":"Cripto favors chondrocyte hypertrophy via TGF-beta SMAD1\/5 signaling during development of osteoarthritis","volume":"255","author":"Vinuesa","year":"2021","journal-title":"The Journal of Pathology"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.molcel.2016.05.027","type":"journal-article","article-title":"Autophagy regulates chromatin ubiquitination in DNA damage response through elimination of SQSTM1\/p62","volume":"63","author":"Wang","year":"2016","journal-title":"Molecular Cell"},{"key":"bib72","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2022.104676","type":"journal-article","article-title":"GATA4 promotes the senescence of nucleus pulposus cells via NF-\u03baB pathway","volume":"101","author":"Wang","year":"2022","journal-title":"Archives of Gerontology and Geriatrics"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.joca.2021.01.008","type":"journal-article","article-title":"Increased IL-6 receptor expression and signaling in ageing cartilage can be explained by loss of TGF-\u03b2-mediated IL-6 receptor suppression","volume":"29","author":"Wiegertjes","year":"2021","journal-title":"Osteoarthritis and Cartilage"},{"key":"bib74","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.933015","type":"journal-article","article-title":"DNA damage response and GATA4 signaling in cellular senescence and aging-related pathology","volume":"14","author":"Xiong","year":"2022","journal-title":"Frontiers in Aging Neuroscience"},{"key":"bib75","doi-asserted-by":"publisher","DOI":"10.1126\/science.adt0548","type":"journal-article","article-title":"Osteoarthritis treatment via the GLP-1-mediated gut-joint axis targets intestinal FXR signaling","volume":"388","author":"Yang","year":"2025","journal-title":"Science"},{"key":"bib76","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01330-w","type":"journal-article","article-title":"Osteoarthritis: pathogenic signaling pathways and therapeutic targets","volume":"8","author":"Yao","year":"2023","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0233-3","type":"journal-article","article-title":"Hypoxia and aging","volume":"51","author":"Yeo","year":"2019","journal-title":"Experimental & Molecular Medicine"},{"key":"bib78","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62852","type":"journal-article","article-title":"DNA damage-how and why we age?","volume":"10","author":"Yousefzadeh","year":"2021","journal-title":"eLife"},{"key":"bib79","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.927126","type":"journal-article","article-title":"HIF-1\u03b1 in osteoarthritis: from pathogenesis to therapeutic implications","volume":"13","author":"Zeng","year":"2022","journal-title":"Frontiers in Pharmacology"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"3620","DOI":"10.3892\/etm.2020.8618","type":"journal-article","article-title":"Matrix metalloproteinase-13, NF-\u03baB p65 and interleukin-1\u03b2 are associated with the severity of knee osteoarthritis","volume":"19","author":"Zhao","year":"2020","journal-title":"Experimental and Therapeutic Medicine"},{"key":"dataset1","type":"dataset","article-title":"Aging-associated Increase of GATA4 levels in Articular Cartilage is Linked to Impaired Regenerative Capacity of Chondrocytes and Osteoarthritis","volume-title":"NCBI Gene Expression Omnibus","author":"Makarczyk","year":"2025","unstructured":"Makarczyk M, Zhang Y, Aguglia A, Bartholomew O, Hines S, Sinkar S, Liu S, Duvall C, Lin H. 2025. Aging-associated Increase of GATA4 levels in Articular Cartilage is Linked to Impaired Regenerative Capacity of Chondrocytes and Osteoarthritis. NCBI Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=gse287861. GSE287861."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/106224\/elife-106224-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/106224\/elife-106224-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/106224","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:53:45Z","timestamp":1787561625000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/106224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":81,"alternative-id":["10.7554\/eLife.106224"],"URL":"https:\/\/doi.org\/10.7554\/elife.106224","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.03.18.643933","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.106224.4","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.106224.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.106224.2","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.106224.3","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE287861","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP106224"}}