{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:15:44Z","timestamp":1788448544457,"version":"build-2803163510"},"reference-count":103,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100029628","name":"Knee Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100029628","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013738","name":"Pacira Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018275","name":"American Association of Hip and Knee Surgeons","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018275","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100032294","name":"Hip Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100032294","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","theclinics.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Orthopedic Clinics of North America"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.ocl.2026.05.003","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:48:26Z","timestamp":1782938906000},"page":"307-316","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in Gene Therapy for Osteoarthritis"],"prefix":"10.1016","volume":"57","author":[{"suffix":"Jr.","given":"J. Michael","family":"Ruth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Mihalko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Holland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10264","key":"10.1016\/j.ocl.2026.05.003_bib1","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/S0140-6736(20)32230-3","article-title":"Osteoarthritis in 2020 and beyond: a lancet commission","volume":"396","author":"Hunter","year":"2020","journal-title":"Lancet"},{"issue":"12","key":"10.1016\/j.ocl.2026.05.003_bib3","doi-asserted-by":"crossref","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 (Hoboken)"},{"issue":"8","key":"10.1016\/j.ocl.2026.05.003_bib4","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.joca.2015.04.008","article-title":"The substantial personal burden experienced by younger people with hip or knee osteoarthritis","volume":"23","author":"Ackerman","year":"2015","journal-title":"Osteoarthr Cartil"},{"issue":"3","key":"10.1016\/j.ocl.2026.05.003_bib5","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2106\/JBJS.J.01958","article-title":"The dramatic increase in total knee replacement utilization rates in the United States cannot be fully explained by growth in population size and the obesity epidemic","volume":"94","author":"Losina","year":"2012","journal-title":"J Bone Joint Surg Am"},{"issue":"8","key":"10.1016\/j.ocl.2026.05.003_bib6","doi-asserted-by":"crossref","first-page":"635","DOI":"10.7326\/0003-4819-133-8-200010170-00016","article-title":"Osteoarthritis: new insights. Part 1: the disease and its risk factors","volume":"133","author":"Felson","year":"2000","journal-title":"Annals of Internal Medicine"},{"issue":"7","key":"10.1016\/j.ocl.2026.05.003_bib7","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1002\/art.39692","article-title":"Updated projected prevalence of self-reported doctor-diagnosed arthritis and arthritis-attributable activity limitation among US adults, 2015-2040","volume":"68","author":"Hootman","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.ocl.2026.05.003_bib8","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1097\/01.blo.0000188066.01833.4f","article-title":"Changing demographics of patients with total joint replacement","volume":"443","author":"Crowninshield","year":"2006","journal-title":"Clin Orthop Relat Res"},{"issue":"2","key":"10.1016\/j.ocl.2026.05.003_bib9","doi-asserted-by":"crossref","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"},{"issue":"11","key":"10.1016\/j.ocl.2026.05.003_bib10","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1007\/s10067-016-3391-x","article-title":"Risks of acute coronary syndrome in patients with osteoarthritis: a nationwide population-based cohort study","volume":"35","author":"Chung","year":"2016","journal-title":"Clin Rheumatol"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib11","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2016-000344","article-title":"Coronary heart disease is associated with a worse clinical outcome of hand osteoarthritis: a cross-sectional and longitudinal study","volume":"3","author":"Courties","year":"2017","journal-title":"RMD Open"},{"issue":"3","key":"10.1016\/j.ocl.2026.05.003_bib12","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/ageing\/afw216","article-title":"Association between lower limb osteoarthritis and incidence of depressive symptoms: data from the osteoarthritis initiative","volume":"46","author":"Veronese","year":"2017","journal-title":"Age Ageing"},{"issue":"10","key":"10.1016\/j.ocl.2026.05.003_bib13","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1136\/annrheumdis-2015-208056","article-title":"Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women","volume":"75","author":"Kluzek","year":"2016","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"10.1016\/j.ocl.2026.05.003_bib14","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/1941738109350438","article-title":"The basic science of articular cartilage: structure, composition, and function","volume":"1","author":"Sophia Fox","year":"2009","journal-title":"Sports Health"},{"key":"10.1016\/j.ocl.2026.05.003_bib15","series-title":"Injury and repair of the musculoskeletal soft tissues","first-page":"405","article-title":"Articular cartilage: composition and structure","author":"Buckwalter","year":"1988"},{"key":"10.1016\/j.ocl.2026.05.003_bib16","first-page":"477","article-title":"Articular cartilage: tissue design and chondrocyte-matrix interactions","volume":"47","author":"Buckwalter","year":"1998","journal-title":"Instr Course Lect"},{"key":"10.1016\/j.ocl.2026.05.003_bib17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.semcdb.2016.10.004","article-title":"Transcriptional control of chondrocyte specification and differentiation","volume":"62","author":"Liu","year":"2017","journal-title":"Semin Cell Dev Biol"},{"issue":"6937","key":"10.1016\/j.ocl.2026.05.003_bib18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nature01657","article-title":"Developmental regulation of the growth plate","volume":"423","author":"Kronenberg","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.ocl.2026.05.003_bib19","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.79925","article-title":"Lineage-specific differences and regulatory networks governing human chondrocyte development","volume":"12","author":"Richard","year":"2023","journal-title":"eLife"},{"issue":"10","key":"10.1016\/j.ocl.2026.05.003_bib20","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.joca.2020.05.009","article-title":"Lubricin in experimental and naturally occurring osteoarthritis: a systematic review","volume":"28","author":"Watkins","year":"2020","journal-title":"Osteoarthr Cartil"},{"issue":"15","key":"10.1016\/j.ocl.2026.05.003_bib21","doi-asserted-by":"crossref","first-page":"5852","DOI":"10.1073\/pnas.1219289110","article-title":"Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis","volume":"110","author":"Waller","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"10.1016\/j.ocl.2026.05.003_bib22","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1172\/JCI200522263","article-title":"The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth","volume":"115","author":"Rhee","year":"2005","journal-title":"J Clin Investig"},{"issue":"3","key":"10.1016\/j.ocl.2026.05.003_bib23","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.rehab.2016.03.005","article-title":"Altered joint tribology in osteoarthritis: reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches","volume":"59","author":"Szychlinska","year":"2016","journal-title":"Ann Phys Rehabil Med"},{"issue":"2","key":"10.1016\/j.ocl.2026.05.003_bib24","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1042\/BJ20100360","article-title":"The glycosylation of human synovial lubricin: implications for its role in inflammation","volume":"429","author":"Estrella","year":"2010","journal-title":"Biochem J"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib25","doi-asserted-by":"crossref","DOI":"10.1080\/21655979.2025.2501880","article-title":"Molecular signaling pathways in osteoarthritis and biomaterials for cartilage regeneration: a review","volume":"16","author":"Hiruthyaswamy","year":"2025","journal-title":"Bioengineered"},{"issue":"4","key":"10.1016\/j.ocl.2026.05.003_bib26","doi-asserted-by":"crossref","first-page":"410","DOI":"10.3899\/jrheum.160226","article-title":"The effect of aging and mechanical loading on the metabolism of articular cartilage","volume":"44","author":"J\u00f8rgensen","year":"2017","journal-title":"J Rheumatol"},{"issue":"7","key":"10.1016\/j.ocl.2026.05.003_bib27","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0254383","article-title":"Reduction of knee joint load suppresses cartilage degeneration, osteophyte formation, and synovitis in early-stage osteoarthritis using a post-traumatic rat model","volume":"16","author":"Takahashi","year":"2021","journal-title":"PLoS One"},{"issue":"4","key":"10.1016\/j.ocl.2026.05.003_bib28","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1177\/1947603513495889","article-title":"The roles of mechanical stresses in the pathogenesis of osteoarthritis: implications for treatment of joint injuries","volume":"4","author":"Buckwalter","year":"2013","journal-title":"Cartilage"},{"issue":"8","key":"10.1016\/j.ocl.2026.05.003_bib29","doi-asserted-by":"crossref","first-page":"542","DOI":"10.2174\/138920208786847953","article-title":"Genetics in osteoarthritis","volume":"9","author":"Fern\u00e1ndez-Moreno","year":"2008","journal-title":"Curr Genomics"},{"issue":"12","key":"10.1016\/j.ocl.2026.05.003_bib30","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25126352","article-title":"The role of MicroRNAs in the pathophysiology of osteoarthritis","volume":"25","author":"Szala","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib31","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrrheum.2014.162","article-title":"Emerging regulators of the inflammatory process in osteoarthritis","volume":"11","author":"Liu-Bryan","year":"2015","journal-title":"Nat Rev Rheumatol"},{"issue":"10","key":"10.1016\/j.ocl.2026.05.003_bib32","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nrrheum.2016.136","article-title":"Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis","volume":"12","author":"Robinson","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"10.1016\/j.ocl.2026.05.003_bib33","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.bone.2016.01.019","article-title":"Inflammatory mediators in osteoarthritis: a critical review of the state-of-the-art, current prospects, and future challenges","volume":"85","author":"Rahmati","year":"2016","journal-title":"Bone"},{"key":"10.1016\/j.ocl.2026.05.003_bib34","article-title":"Interleukins, growth factors, and transcription factors are key targets for gene therapy in osteoarthritis: a scoping review","volume":"10","author":"Uebelhoer","year":"2023","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.bbapap.2011.06.020","article-title":"Proteases involved in cartilage matrix degradation in osteoarthritis","volume":"1824","author":"Troeberg","year":"2012","journal-title":"Biochim Biophys Acta"},{"issue":"5","key":"10.1016\/j.ocl.2026.05.003_bib36","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41584-022-00749-9","article-title":"Synovial inflammation in osteoarthritis progression","volume":"18","author":"Sanchez-Lopez","year":"2022","journal-title":"Nat Rev Rheumatol"},{"issue":"6","key":"10.1016\/j.ocl.2026.05.003_bib37","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.jbspin.2013.09.007","article-title":"Is osteoarthritis a metabolic disease?","volume":"80","author":"Sellam","year":"2013","journal-title":"Jt Bone Spine"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib38","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/bmb\/ldv028","article-title":"Is osteoarthritis a metabolic disorder?","volume":"115","author":"Kluzek","year":"2015","journal-title":"Br Med Bull"},{"issue":"12","key":"10.1016\/j.ocl.2026.05.003_bib39","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1002\/jor.23420","article-title":"Emerging role of metabolic signaling in synovial joint remodeling and osteoarthritis","volume":"34","author":"June","year":"2016","journal-title":"J Orthop Res"},{"issue":"5","key":"10.1016\/j.ocl.2026.05.003_bib40","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nrrheum.2017.50","article-title":"The role of metabolism in the pathogenesis of osteoarthritis","volume":"13","author":"Mobasheri","year":"2017","journal-title":"Nat Rev Rheumatol"},{"issue":"4","key":"10.1016\/j.ocl.2026.05.003_bib41","first-page":"285","article-title":"Pathogenetic mechanisms of posttraumatic osteoarthritis: opportunities for early intervention","volume":"4","author":"Kramer","year":"2011","journal-title":"Int J Clin Exp Med"},{"issue":"9","key":"10.1016\/j.ocl.2026.05.003_bib42","doi-asserted-by":"crossref","first-page":"e721","DOI":"10.5435\/JAAOS-D-21-01233","article-title":"AAOS Clinical Practice Guideline Summary: management of Osteoarthritis of the Knee (Nonarthroplasty), 3rd edition","volume":"30","author":"Brophy","year":"2022","journal-title":"J Am Acad Orthop Surg"},{"issue":"20","key":"10.1016\/j.ocl.2026.05.003_bib43","doi-asserted-by":"crossref","first-page":"e1027","DOI":"10.5435\/JAAOS-D-24-00420","article-title":"American Academy of Orthopaedic Surgeons Clinical Practice Guideline Summary management of osteoarthritis of the hip","volume":"32","author":"Hannon","year":"2024","journal-title":"J Am Acad Orthop Surg"},{"issue":"24","key":"10.1016\/j.ocl.2026.05.003_bib44","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.5435\/JAAOS-D-23-00338","article-title":"American Academy of Orthopaedic Surgeons Clinical Practice Guideline Summary of surgical management of osteoarthritis of the knee","volume":"31","author":"Srivastava","year":"2023","journal-title":"J Am Acad Orthop Surg"},{"issue":"9","key":"10.1016\/j.ocl.2026.05.003_bib45","doi-asserted-by":"crossref","first-page":"726","DOI":"10.7326\/0003-4819-133-9-200011070-00015","article-title":"Osteoarthritis: new insights. Part 2: treatment approaches","volume":"133","author":"Felson","year":"2000","journal-title":"Ann Intern Med"},{"issue":"12","key":"10.1016\/j.ocl.2026.05.003_bib46","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41584-020-00518-6","article-title":"Emerging pharmaceutical therapies for osteoarthritis","volume":"16","author":"Latourte","year":"2020","journal-title":"Nat Rev Rheumatol"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib47","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s40122-021-00350-0","article-title":"Satisfaction with medications prescribed for Osteoarthritis: a Cross-Sectional Survey of patients and their physicians in the United States","volume":"11","author":"Robinson","year":"2022","journal-title":"Pain Ther"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.ocarto.2020.100032","article-title":"Satisfaction after total knee replacement for osteoarthritis is usually high, but what are we measuring? A systematic review","volume":"2","author":"Klem","year":"2020","journal-title":"Osteoarthr Cartil Open"},{"issue":"2 Suppl","key":"10.1016\/j.ocl.2026.05.003_bib49","first-page":"s227","article-title":"Future treatment of osteoarthritis","volume":"28","author":"Baker","year":"2005","journal-title":"Orthopedics"},{"issue":"4","key":"10.1016\/j.ocl.2026.05.003_bib50","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/sj.gt.3302196","article-title":"Osteoarthritis gene therapy","volume":"11","author":"Evans","year":"2004","journal-title":"Gene Ther"},{"issue":"8","key":"10.1016\/j.ocl.2026.05.003_bib51","doi-asserted-by":"crossref","DOI":"10.2106\/JBJS.RVW.20.00220","article-title":"Orthopaedic gene therapy: Twenty-Five years on","volume":"9","author":"Evans","year":"2021","journal-title":"JBJS Rev"},{"issue":"4","key":"10.1016\/j.ocl.2026.05.003_bib52","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrrheum.2015.28","article-title":"Gene therapy approaches to regenerating the musculoskeletal system","volume":"11","author":"Evans","year":"2015","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"10.1016\/j.ocl.2026.05.003_bib53","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/jgm.2698","article-title":"Gene therapy clinical trials worldwide to 2012 - an update","volume":"15","author":"Ginn","year":"2013","journal-title":"J Gene Med"},{"issue":"5644","key":"10.1016\/j.ocl.2026.05.003_bib54","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1126\/science.1088547","article-title":"LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1","volume":"302","author":"Hacein-Bey-Abina","year":"2003","journal-title":"Science (New York, N.Y.)"},{"issue":"1\u20132","key":"10.1016\/j.ocl.2026.05.003_bib55","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ymgme.2003.08.016","article-title":"Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer","volume":"80","author":"Raper","year":"2003","journal-title":"Mol Genet Metabol"},{"issue":"10","key":"10.1016\/j.ocl.2026.05.003_bib56","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.5435\/JAAOS-D-15-00339","article-title":"Emerging concepts in gene therapy for osteoarthritis","volume":"23","author":"Rai","year":"2015","journal-title":"J Am Acad Orthop Surg"},{"issue":"2","key":"10.1016\/j.ocl.2026.05.003_bib57","doi-asserted-by":"crossref","DOI":"10.1093\/pcmedi\/pbad014","article-title":"New treatment for osteoarthritis: gene therapy","volume":"6","author":"Li","year":"2023","journal-title":"Precis Clin Med"},{"issue":"10","key":"10.1016\/j.ocl.2026.05.003_bib58","article-title":"Advances in biomaterial-mediated gene therapy for articular cartilage repair","volume":"9","author":"Zhu","year":"2022","journal-title":"Bioengineering (Basel)"},{"key":"10.1016\/j.ocl.2026.05.003_bib59","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.2147\/DDDT.S432056","article-title":"Biomaterial-based gene delivery: advanced tools for enhanced cartilage regeneration","volume":"17","author":"Chen","year":"2023","journal-title":"Drug Des Dev Ther"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib60","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1097\/BOR.0000000000000918","article-title":"Osteoarthritis gene therapy in 2022","volume":"35","author":"Evans","year":"2023","journal-title":"Curr Opin Rheumatol"},{"issue":"23","key":"10.1016\/j.ocl.2026.05.003_bib61","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.5435\/JAAOS-D-24-00831","article-title":"The 2024 OREF clinical research award: progress toward a gene therapy for arthritis","volume":"32","author":"Evans","year":"2024","journal-title":"J Am Acad Orthop Surg"},{"issue":"5","key":"10.1016\/j.ocl.2026.05.003_bib62","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1080\/03008207.2025.2533332","article-title":"Application of gene therapy in osteoarthritis","volume":"66","author":"Li","year":"2025","journal-title":"Connect Tissue Res"},{"issue":"5","key":"10.1016\/j.ocl.2026.05.003_bib63","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1080\/03008207.2025.2520319","article-title":"Gene therapy pipelines for osteoarthritis: current innovations, operational challenges, and future directions","volume":"66","author":"Peitso","year":"2025","journal-title":"Connect Tissue Res"},{"issue":"Pt B","key":"10.1016\/j.ocl.2026.05.003_bib64","article-title":"RNF125, transcriptionally regulated by NFATC2, alleviates osteoarthritis via inhibiting the Wnt\/beta-catenin signaling pathway through degrading TRIM14","volume":"125","author":"Lv","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"10.1016\/j.ocl.2026.05.003_bib65","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms13336","article-title":"Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes","volume":"7","author":"Kobayashi","year":"2016","journal-title":"Nat Commun"},{"issue":"176","key":"10.1016\/j.ocl.2026.05.003_bib66","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3005409","article-title":"Proteoglycan 4 expression protects against the development of osteoarthritis","volume":"5","author":"Ruan","year":"2013","journal-title":"Sci Transl Med"},{"issue":"12","key":"10.1016\/j.ocl.2026.05.003_bib67","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1016\/j.cellsig.2015.09.004","article-title":"Suppression of Nkx3.2 by phosphatidylinositol-3-kinase signaling regulates cartilage development by modulating chondrocyte hypertrophy","volume":"27","author":"Kim","year":"2015","journal-title":"Cell Signal"},{"issue":"3","key":"10.1016\/j.ocl.2026.05.003_bib68","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/ncb1538","article-title":"Constitutive RelA activation mediated by Nkx3.2 controls chondrocyte viability","volume":"9","author":"Park","year":"2007","journal-title":"Nat Cell Biol"},{"issue":"14","key":"10.1016\/j.ocl.2026.05.003_bib69","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1128\/MCB.00253-10","article-title":"Exogenous signal-independent nuclear IkappaB kinase activation triggered by Nkx3.2 enables constitutive nuclear degradation of IkappaB-alpha in chondrocytes","volume":"31","author":"Yong","year":"2011","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.ocl.2026.05.003_bib70","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2022.901317","article-title":"Gene therapy in orthopaedics: progress and challenges in pre-clinical development and translation","volume":"10","author":"Watson-Levings","year":"2022","journal-title":"Front Bioeng Biotechnol"},{"issue":"15","key":"10.1016\/j.ocl.2026.05.003_bib71","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.7150\/ijms.56760","article-title":"Cellular and tissue selectivity of AAV serotypes for gene delivery to chondrocytes and cartilage","volume":"18","author":"Yoon","year":"2021","journal-title":"Int J Med Sci"},{"key":"10.1016\/j.ocl.2026.05.003_bib72","doi-asserted-by":"crossref","DOI":"10.1038\/mtm.2016.8","article-title":"Treatment of osteoarthritis using a helper-dependent adenoviral vector retargeted to chondrocytes","volume":"3","author":"Ruan","year":"2016","journal-title":"Mol Ther Methods Clin Dev"},{"issue":"4","key":"10.1016\/j.ocl.2026.05.003_bib73","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41576-019-0205-4","article-title":"Engineering adeno-associated virus vectors for gene therapy","volume":"21","author":"Li","year":"2020","journal-title":"Nat Rev Genet"},{"key":"10.1016\/j.ocl.2026.05.003_bib74","article-title":"AAV vectors: an emerging strategy for chronic pain management","author":"Nassini","year":"2025","journal-title":"Trends Mol Med"},{"issue":"11","key":"10.1016\/j.ocl.2026.05.003_bib75","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1002\/art.40668","article-title":"Disease-modifying osteoarthritis treatment with Interleukin-1 receptor antagonist gene therapy in small and large animal models","volume":"70","author":"Nixon","year":"2018","journal-title":"Arthritis Rheumatol"},{"issue":"12","key":"10.1016\/j.ocl.2026.05.003_bib76","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics16121518","article-title":"The intra-articular delivery of a low-dose adeno-associated Virus-IL-1 receptor antagonist vector alleviates the progress of arthritis in an osteoarthritis rat model","volume":"16","author":"Luo","year":"2024","journal-title":"Pharmaceutics"},{"issue":"2","key":"10.1016\/j.ocl.2026.05.003_bib77","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41434-024-00504-7","article-title":"PCRX-201, a novel IL-1Ra gene therapy treatment approach for low back pain resulting from intervertebral disc degeneration","volume":"32","author":"Snuggs","year":"2025","journal-title":"Gene Ther"},{"key":"10.1016\/j.ocl.2026.05.003_bib78","doi-asserted-by":"crossref","DOI":"10.1038\/mtm.2015.52","article-title":"Safety and biodistribution assessment of sc-rAAV2.5IL-1Ra administered via intra-articular injection in a mono-iodoacetate-induced osteoarthritis rat model","volume":"3","author":"Wang","year":"2016","journal-title":"Mol Ther Methods Clin Dev"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib79","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1089\/hum.2017.181","article-title":"Gene delivery to joints by intra-articular injection","volume":"29","author":"Evans","year":"2018","journal-title":"Hum Gene Ther"},{"issue":"2","key":"10.1016\/j.ocl.2026.05.003_bib80","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1089\/humc.2017.142","article-title":"Gene therapy for osteoarthritis: pharmacokinetics of intra-articular self-complementary adeno-associated virus Interleukin-1 receptor antagonist delivery in an equine model","volume":"29","author":"Watson Levings","year":"2018","journal-title":"Hum Gene Ther Clin Dev"},{"issue":"801","key":"10.1016\/j.ocl.2026.05.003_bib81","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adu9804","article-title":"A phase 1 clinical trial shows safe, sustained, AAV-mediated expression of IL-1Ra in the human osteoarthritic knee joint","volume":"17","author":"De la Vega","year":"2025","journal-title":"Sci Transl Med"},{"issue":"13","key":"10.1016\/j.ocl.2026.05.003_bib82","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1177\/03635465211049414","article-title":"rAAV-Mediated sox9 overexpression improves the repair of osteochondral defects in a clinically relevant large animal model over time in vivo and reduces perifocal osteoarthritic changes","volume":"49","author":"Lange","year":"2021","journal-title":"Am J Sports Med"},{"issue":"4","key":"10.1016\/j.ocl.2026.05.003_bib83","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1177\/0363546521988941","article-title":"rAAV-Mediated human FGF-2 gene therapy enhances osteochondral repair in a clinically relevant large animal model over time in vivo","volume":"49","author":"Morscheid","year":"2021","journal-title":"Am J Sports Med"},{"issue":"9\u201310","key":"10.1016\/j.ocl.2026.05.003_bib84","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1089\/hum.2021.177","article-title":"Intra-articular adeno-associated virus-mediated proteoglycan 4 gene therapy for preventing posttraumatic osteoarthritis","volume":"33","author":"Seol","year":"2022","journal-title":"Hum Gene Ther"},{"issue":"5","key":"10.1016\/j.ocl.2026.05.003_bib85","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1177\/03635465241235149","article-title":"Locally directed recombinant Adeno- associated virus-mediated IGF-1 gene therapy enhances osteochondral repair and counteracts early osteoarthritis in vivo","volume":"52","author":"Peifer","year":"2024","journal-title":"Am J Sports Med"},{"key":"10.1016\/j.ocl.2026.05.003_bib86","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2020.598466","article-title":"Non-viral gene delivery methods for bone and joints","volume":"8","author":"Gantenbein","year":"2020","journal-title":"Front Bioeng Biotechnol"},{"key":"10.1016\/j.ocl.2026.05.003_bib87","article-title":"Non-viral gene therapy for osteoarthritis","volume":"8","author":"Uzieliene","year":"2020","journal-title":"Front Bioeng Biotechnol"},{"issue":"10","key":"10.1016\/j.ocl.2026.05.003_bib88","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics17101272","article-title":"The application of novel drug delivery systems in the treatment of osteoarthritis","volume":"17","author":"Huang","year":"2025","journal-title":"Pharmaceutics"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib89","doi-asserted-by":"crossref","first-page":"9184","DOI":"10.1038\/s41467-025-64212-5","article-title":"Virus-inspired lipopeptide-derived nucleic acid delivery to cartilage for osteoarthritis therapy","volume":"16","author":"Fu","year":"2025","journal-title":"Nat Commun"},{"key":"10.1016\/j.ocl.2026.05.003_bib90","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.3389\/fphar.2019.01534","article-title":"Scaffold-based gene therapeutics for osteochondral tissue engineering","volume":"10","author":"Yan","year":"2019","journal-title":"Front Pharmacol"},{"issue":"12","key":"10.1016\/j.ocl.2026.05.003_bib91","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1016\/j.joca.2015.06.019","article-title":"Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-beta1 in patients with grade 3 chronic degenerative joint disease of the knee","volume":"23","author":"Cherian","year":"2015","journal-title":"Osteoarthr Cartil"},{"issue":"2","key":"10.1016\/j.ocl.2026.05.003_bib92","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1089\/humc.2014.145","article-title":"A multicenter, single-blind, phase IIa clinical trial to evaluate the efficacy and safety of a cell-mediated gene therapy in degenerative knee arthritis patients","volume":"26","author":"Ha","year":"2015","journal-title":"Hum Gene Ther Clin Dev"},{"issue":"12","key":"10.1016\/j.ocl.2026.05.003_bib93","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.joca.2023.07.008","article-title":"TissueGene-C induces long-term analgesic effects through regulation of pain mediators and neuronal sensitization in a rat monoiodoacetate-induced model of osteoarthritis pain","volume":"31","author":"Park","year":"2023","journal-title":"Osteoarthr Cartil"},{"issue":"1","key":"10.1016\/j.ocl.2026.05.003_bib94","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/03008207.2016.1208655","article-title":"Inflammation and epigenetic regulation in osteoarthritis","volume":"58","author":"Shen","year":"2017","journal-title":"Connect Tissue Res"},{"key":"10.1016\/j.ocl.2026.05.003_bib95","doi-asserted-by":"crossref","DOI":"10.1016\/j.joca.2016.01.581","article-title":"Generation of IL1\u03b2-resistant chondrocytes using CRISPR-CAS genome editing","volume":"24","author":"Karlsen","year":"2016","journal-title":"Osteoarthr Cartil"},{"issue":"17","key":"10.1016\/j.ocl.2026.05.003_bib96","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21176046","article-title":"Emerging gene-editing modalities for osteoarthritis","volume":"21","author":"Tanikella","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"13","key":"10.1016\/j.ocl.2026.05.003_bib97","doi-asserted-by":"crossref","first-page":"3643","DOI":"10.1016\/j.celrep.2019.02.088","article-title":"Maintenance of nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis","volume":"26","author":"Ren","year":"2019","journal-title":"Cell Rep"},{"issue":"7\u20138","key":"10.1016\/j.ocl.2026.05.003_bib98","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41434-020-0149-5","article-title":"Treating osteoarthritis via gene therapy with rejuvenation factors","volume":"27","author":"Zhang","year":"2020","journal-title":"Gene Ther"},{"key":"10.1016\/j.ocl.2026.05.003_bib99","article-title":"MiR-210 inhibits NF-kappaB signaling pathway by targeting DR6 in osteoarthritis","volume":"5","author":"Zhang","year":"2015","journal-title":"Sci Rep"},{"issue":"10","key":"10.1016\/j.ocl.2026.05.003_bib100","article-title":"microRNA-140 inhibits inflammation and stimulates chondrogenesis in a model of interleukin 1beta-induced osteoarthritis","volume":"5","author":"Karlsen","year":"2016","journal-title":"Mol Ther Nucleic Acids"},{"issue":"8","key":"10.1016\/j.ocl.2026.05.003_bib101","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1302\/2046-3758.148.BJR-2024-0267.R4","article-title":"Comparisons of miRNA profiles of exosomes derived from human iPSCs, ADSCs, and BMSCs and effects on chondrocyte function","volume":"14","author":"Chang","year":"2025","journal-title":"Bone Joint Res"},{"key":"10.1016\/j.ocl.2026.05.003_bib102","article-title":"Integrated analysis of miRNAs and gene expression profiles reveals potential biomarkers for osteoarthritis","volume":"13","author":"Li","year":"2022","journal-title":"Front Genet"},{"issue":"10","key":"10.1016\/j.ocl.2026.05.003_bib103","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1016\/j.joca.2017.06.002","article-title":"Intra-articular injection of microRNA-140 (miRNA-140) alleviates osteoarthritis (OA) progression by modulating extracellular matrix (ECM) homeostasis in rats","volume":"25","author":"Si","year":"2017","journal-title":"Osteoarthr Cartil"},{"key":"10.1016\/j.ocl.2026.05.003_bib104","doi-asserted-by":"crossref","first-page":"9609","DOI":"10.2147\/JIR.S529149","article-title":"Mechanosensitive miRNAs in cartilage and subchondral bone remodeling: emerging targets for osteoarthritis therapy","volume":"18","author":"Shang","year":"2025","journal-title":"J Inflamm Res"}],"container-title":["Orthopedic Clinics of North America"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0030589826000738?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0030589826000738?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:30:25Z","timestamp":1788445825000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0030589826000738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":103,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["S0030589826000738"],"URL":"https:\/\/doi.org\/10.1016\/j.ocl.2026.05.003","relation":{},"ISSN":["0030-5898"],"issn-type":[{"value":"0030-5898","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Advances in Gene Therapy for Osteoarthritis","name":"articletitle","label":"Article Title"},{"value":"Orthopedic Clinics of North America","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ocl.2026.05.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}