{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:19:25Z","timestamp":1793161165953,"version":"4.5.0"},"reference-count":217,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372374"],"award-info":[{"award-number":["82372374"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Bone Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) is a highly heterogeneous disease that exhibits distinct clinical manifestations and pathological mechanisms in different joints, patients, and even at different disease stages for the same patient. Genetic and pathophysiological factors contribute to the heterogeneity of OA in clinical manifestations, treatment responses, and prognosis of patients. Despite efforts in developing disease-modifying OA drugs and treatment technologies, no current approach can efficiently delay OA progression, and results from clinical research are inconsistent due to the mismatch between treatment mechanisms and heterogeneous patient subtypes. Researchers utilize clinical data to classify OA into different phenotypes based on etiological factors, clinical symptoms, and imaging features, as well as endotypes based on biomarkers, molecular mechanisms, metabolism profiles, and omics analyses, but there is still a lack of unified standards. Therefore, a comprehensive understanding of the heterogeneity and classification of OA is crucial for stratified and personalized treatment. In this Review, we discuss the heterogeneity of OA, with an emphasis on heterogeneity in treatment responses. We provide a structured analysis of current studies of OA classification, offering new perspectives for future OA research and clinical practice.<\/jats:p>","DOI":"10.1038\/s41413-026-00549-x","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T08:06:40Z","timestamp":1783411600000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Advances in heterogeneity and classification of osteoarthritis"],"prefix":"10.1038","volume":"14","author":[{"given":"Taiyuan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiong","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoran","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6009-629X","authenticated-orcid":false,"given":"Zhong Alan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocky S.","family":"Tuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9479-730X","authenticated-orcid":false,"given":"Changhai","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7650-4828","authenticated-orcid":false,"given":"Yao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"549_CR1","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1136\/ard-2023-225324","volume":"83","author":"Q Weng","year":"2024","unstructured":"Weng, Q. et al. Global burden of early-onset osteoarthritis, 1990-2019: results from the Global Burden of Disease Study 2019. Ann. Rheum. Dis. 83, 915\u2013925 (2024).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41572-025-00594-6","volume":"11","author":"S Tang","year":"2025","unstructured":"Tang, S. et al. Osteoarthritis. Nat. Rev. Dis. Prim. 11, 10 (2025).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"549_CR3","doi-asserted-by":"publisher","first-page":"15365","DOI":"10.3390\/ijms232315365","volume":"23","author":"DA Hart","year":"2022","unstructured":"Hart, D. A. Osteoarthritis as an Umbrella Term for Different Subsets of Humans Undergoing Joint Degeneration: The Need to Address the Differences to Develop Effective Conservative Treatments and Prevention Strategies. Int J. Mol. Sci. 23, 15365 (2022).","journal-title":"Int J. Mol. Sci."},{"key":"549_CR4","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1016\/j.joca.2009.04.014","volume":"17","author":"DJ Hunter","year":"2009","unstructured":"Hunter, D. J. Risk stratification for knee osteoarthritis progression: a narrative review. Osteoarthr. Cartil. 17, 1402\u20131407 (2009).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR5","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.joca.2021.03.002","volume":"30","author":"G Aubourg","year":"2022","unstructured":"Aubourg, G., Rice, S. J., Bruce-Wootton, P. & Loughlin, J. Genetics of osteoarthritis. Osteoarthr. Cartil. 30, 636\u2013649 (2022).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR6","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/s41584-018-0073-x","volume":"14","author":"F Berenbaum","year":"2018","unstructured":"Berenbaum, F., Wallace, I. J., Lieberman, D. E. & Felson, D. T. Modern-day environmental factors in the pathogenesis of osteoarthritis. Nat. Rev. Rheumatol. 14, 674\u2013681 (2018).","journal-title":"Nat. Rev. Rheumatol."},{"key":"549_CR7","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/j.joca.2022.02.614","volume":"30","author":"FW Roemer","year":"2022","unstructured":"Roemer, F. W. et al. Heterogeneity of cartilage damage in Kellgren and Lawrence grade 2 and 3 knees: the MOST study. Osteoarthr. Cartil. 30, 714\u2013723 (2022).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR8","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41392-023-01330-w","volume":"8","author":"Q Yao","year":"2023","unstructured":"Yao, Q. et al. Osteoarthritis: pathogenic signaling pathways and therapeutic targets. Signal Transduct. Target Ther. 8, 56 (2023).","journal-title":"Signal Transduct. Target Ther."},{"key":"549_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocarto.2025.100571","volume":"7","author":"PA Dennis","year":"2025","unstructured":"Dennis, P. A., Anderson, L., Coffman, C. J., Webb, S. & Allen, K. D. Exploration of heterogeneity of treatment effects across exercise-based interventions for knee osteoarthritis. Osteoarthr. Cartil. Open 7, 100571 (2025).","journal-title":"Osteoarthr. Cartil. Open"},{"key":"549_CR10","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/s41413-022-00226-9","volume":"10","author":"L Tong","year":"2022","unstructured":"Tong, L. et al. Current understanding of osteoarthritis pathogenesis and relevant new approaches. Bone Res 10, 60 (2022).","journal-title":"Bone Res"},{"key":"549_CR11","doi-asserted-by":"publisher","first-page":"F1000","DOI":"10.12688\/f1000research.20575.1","volume":"8","author":"A Mobasheri","year":"2019","unstructured":"Mobasheri, A. et al. Recent advances in understanding the phenotypes of osteoarthritis. F1000Research 8, F1000 (2019).","journal-title":"F1000Research"},{"key":"549_CR12","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.molmed.2005.02.005","volume":"11","author":"CA Peach","year":"2005","unstructured":"Peach, C. A., Carr, A. J. & Loughlin, J. Recent advances in the genetic investigation of osteoarthritis. Trends Mol. Med. 11, 186\u2013191 (2005).","journal-title":"Trends Mol. Med."},{"key":"549_CR13","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/2042-6410-4-4","volume":"4","author":"BD Boyan","year":"2013","unstructured":"Boyan, B. D. et al. Addressing the gaps: sex differences in osteoarthritis of the knee. Biol. Sex. Differ. 4, 4 (2013).","journal-title":"Biol. Sex. Differ."},{"key":"549_CR14","doi-asserted-by":"publisher","first-page":"3178","DOI":"10.3390\/jcm10143178","volume":"10","author":"M Tschon","year":"2021","unstructured":"Tschon, M., Contartese, D., Pagani, S., Borsari, V. & Fini, M. Gender and Sex Are Key Determinants in Osteoarthritis Not Only Confounding Variables. A Systematic Review of Clinical Data. J. Clin. Med. 10, 3178 (2021).","journal-title":"J. Clin. Med."},{"key":"549_CR15","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s12877-023-03897-z","volume":"23","author":"YJ Huang","year":"2023","unstructured":"Huang, Y. J., Ke, W., Hu, L., Wei, Y. D. & Dong, M. X. Liquid chromatography-mass spectrometry-based metabolomic profiling reveals sex differences of lipid metabolism among the elderly from Southwest China. BMC Geriatr. 23, 156 (2023).","journal-title":"BMC Geriatr."},{"key":"549_CR16","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/2042-6410-3-26","volume":"3","author":"KA Sluka","year":"2012","unstructured":"Sluka, K. A. et al. Neural and psychosocial contributions to sex differences in knee osteoarthritic pain. Biol. Sex. Differ. 3, 26 (2012).","journal-title":"Biol. Sex. Differ."},{"key":"549_CR17","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1056\/NEJM200004063421405","volume":"342","author":"GA Hawker","year":"2000","unstructured":"Hawker, G. A. et al. Differences between men and women in the rate of use of hip and knee arthroplasty. N. Engl. J. Med 342, 1016\u20131022 (2000).","journal-title":"N. Engl. J. Med"},{"key":"549_CR18","first-page":"129","volume":"12","author":"FM Cornelis","year":"2011","unstructured":"Cornelis, F. M., Luyten, F. P. & Lories, R. J. Functional effects of susceptibility genes in osteoarthritis. Discov. Med. 12, 129\u2013139 (2011).","journal-title":"Discov. Med."},{"key":"549_CR19","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1002\/art.27184","volume":"62","author":"HJ Kerkhof","year":"2010","unstructured":"Kerkhof, H. J. et al. A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22. Arthritis Rheum. 62, 499\u2013510 (2010).","journal-title":"Arthritis Rheum."},{"key":"549_CR20","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/j.joca.2024.04.002","volume":"32","author":"NA Segal","year":"2024","unstructured":"Segal, N. A., Nilges, J. M. & Oo, W. M. Sex differences in osteoarthritis prevalence, pain perception, physical function and therapeutics. Osteoarthr. Cartil. 32, 1045\u20131053 (2024).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-025-05420-y","volume":"12","author":"Y Zhang","year":"2025","unstructured":"Zhang, Y. et al. Sexually Dimorphic Profiling of Osteoarthritis: A Comprehensive Metabolomic Dataset. Sci. Data 12, 1105 (2025).","journal-title":"Sci. Data"},{"key":"549_CR22","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.joca.2007.01.018","volume":"15","author":"T Simopoulou","year":"2007","unstructured":"Simopoulou, T. et al. Differential expression of leptin and leptin\u2019s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism. Osteoarthr. Cartil. 15, 872\u2013883 (2007).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR23","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.joca.2007.04.015","volume":"15","author":"O Gualillo","year":"2007","unstructured":"Gualillo, O. Further evidence for leptin involvement in cartilage homeostases. Osteoarthr. Cartil. 15, 857\u2013860 (2007).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR24","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1002\/acr2.11307","volume":"3","author":"ER Vina","year":"2021","unstructured":"Vina, E. R. et al. Use of Complementary and Alternative Therapy for Knee Osteoarthritis: Race and Gender Variations. ACR Open Rheumatol. 3, 660\u2013667 (2021).","journal-title":"ACR Open Rheumatol."},{"key":"549_CR25","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/ng.176","volume":"40","author":"Y Miyamoto","year":"2008","unstructured":"Miyamoto, Y. et al. Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis. Nat. Genet. 40, 994\u2013998 (2008).","journal-title":"Nat. Genet."},{"key":"549_CR26","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1093\/hmg\/ddp053","volume":"18","author":"I Meulenbelt","year":"2009","unstructured":"Meulenbelt, I. et al. Large replication study and meta-analyses of DVWA as an osteoarthritis susceptibility locus in European and Asian populations. Hum. Mol. Genet. 18, 1518\u20131523 (2009).","journal-title":"Hum. Mol. Genet."},{"key":"549_CR27","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.1136\/ard.2008.102236","volume":"68","author":"AM Valdes","year":"2009","unstructured":"Valdes, A. M. et al. Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Ann. Rheum. Dis. 68, 1916\u20131920 (2009).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-73188-z","volume":"14","author":"L Xu","year":"2024","unstructured":"Xu, L. et al. Identification of key hub genes in knee osteoarthritis through integrated bioinformatics analysis. Sci. Rep. 14, 22437 (2024).","journal-title":"Sci. Rep."},{"key":"549_CR29","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1136\/annrheumdis-2020-217834","volume":"80","author":"CG Boer","year":"2021","unstructured":"Boer, C. G. et al. Genome-wide association of phenotypes based on clustering patterns of hand osteoarthritis identify WNT9A as novel osteoarthritis gene. Ann. Rheum. Dis. 80, 367\u2013375 (2021).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR30","doi-asserted-by":"publisher","first-page":"S48","DOI":"10.1016\/j.joca.2022.02.052","volume":"30","author":"P Kreitmaier","year":"2022","unstructured":"Kreitmaier, P. et al. An epigenome-wide view of osteoarthritis in primary tissues. Osteoarthr. Cartil. 30, S48\u2013S48 (2022).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR31","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1002\/art.42316","volume":"75","author":"CM Dunn","year":"2023","unstructured":"Dunn, C. M. et al. Peripheral blood DNA methylation-based machine learning models for prediction of knee osteoarthritis progression: biologic specimens and data from the osteoarthritis initiative and johnston county osteoarthritis project. Arthritis Rheumatol. 75, 28\u201340 (2023).","journal-title":"Arthritis Rheumatol."},{"key":"549_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21593-7","volume":"12","author":"J Steinberg","year":"2021","unstructured":"Steinberg, J. et al. A molecular quantitative trait locus map for osteoarthritis. Nat. Commun. 12, 1309 (2021).","journal-title":"Nat. Commun."},{"key":"549_CR33","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1016\/j.joca.2020.06.001","volume":"28","author":"AK Sorial","year":"2020","unstructured":"Sorial, A. K. et al. Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC. Osteoarthr. Cartil. 28, 1448\u20131458 (2020).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR34","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.joca.2020.01.001","volume":"28","author":"X Duan","year":"2020","unstructured":"Duan, X. et al. RNA-seq analysis of chondrocyte transcriptome reveals genetic heterogeneity in LG\/J and SM\/J murine strains. Osteoarthr. Cartil. 28, 516\u2013527 (2020).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR35","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.semarthrit.2009.03.006","volume":"39","author":"G Herrero-Beaumont","year":"2009","unstructured":"Herrero-Beaumont, G., Roman-Blas, J. A., Casta\u00f1eda, S. & Jimenez, S. A. Primary osteoarthritis no longer primary: three subsets with distinct etiological, clinical, and therapeutic characteristics. Semin. Arthritis Rheum. 39, 71\u201380 (2009).","journal-title":"Semin. Arthritis Rheum."},{"key":"549_CR36","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/nrrheum.2017.50","volume":"13","author":"A Mobasheri","year":"2017","unstructured":"Mobasheri, A. et al. The role of metabolism in the pathogenesis of osteoarthritis. Nat. Rev. Rheumatol. 13, 302\u2013311 (2017).","journal-title":"Nat. Rev. Rheumatol."},{"key":"549_CR37","doi-asserted-by":"publisher","first-page":"iv34","DOI":"10.1093\/rheumatology\/kex417","volume":"57","author":"LA Deveza","year":"2018","unstructured":"Deveza, L. A. & Loeser, R. F. Is osteoarthritis one disease or a collection of many? Rheumatology 57, iv34\u2013iv42 (2018).","journal-title":"Rheumatology"},{"key":"549_CR38","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.21037\/atm-20-4673","volume":"8","author":"C Huang","year":"2020","unstructured":"Huang, C. et al. Development and formulation of the classification criteria for osteoarthritis. Ann. Transl. Med. 8, 1068 (2020).","journal-title":"Ann. Transl. Med."},{"key":"549_CR39","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41413-024-00375-z","volume":"12","author":"Z Han","year":"2024","unstructured":"Han, Z., Wang, K., Ding, S. & Zhang, M. Cross-talk of inflammation and cellular senescence: a new insight into the occurrence and progression of osteoarthritis. Bone Res. 12, 69 (2024).","journal-title":"Bone Res."},{"key":"549_CR40","doi-asserted-by":"publisher","first-page":"5137","DOI":"10.3390\/s24165137","volume":"24","author":"T Taniguchi","year":"2024","unstructured":"Taniguchi, T. et al. Relationship between Fear-Avoidance Beliefs and Muscle Co-Contraction in People with Knee Osteoarthritis. Sensors 24, 5137 (2024).","journal-title":"Sensors"},{"key":"549_CR41","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.joca.2021.09.010","volume":"30","author":"M Hall","year":"2022","unstructured":"Hall, M. et al. How does hip osteoarthritis differ from knee osteoarthritis? Osteoarthr. Cartil. 30, 32\u201341 (2022).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR42","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/s41584-021-00747-3","volume":"18","author":"M Favero","year":"2022","unstructured":"Favero, M. et al. Erosive hand osteoarthritis: latest findings and outlook. Nat. Rev. Rheumatol. 18, 171\u2013183 (2022).","journal-title":"Nat. Rev. Rheumatol."},{"key":"549_CR43","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1016\/j.joca.2017.01.015","volume":"25","author":"X Jin","year":"2017","unstructured":"Jin, X. et al. Associations between endogenous sex hormones and MRI structural changes in patients with symptomatic knee osteoarthritis. Osteoarthr. Cartil. 25, 1100\u20131106 (2017).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR44","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1136\/ard.2011.150243","volume":"70","author":"FW Roemer","year":"2011","unstructured":"Roemer, F. W. et al. Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study. Ann. Rheum. Dis. 70, 1804\u20131809 (2011).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR45","doi-asserted-by":"publisher","first-page":"501","DOI":"10.3899\/jrheum.130541","volume":"41","author":"A Guermazi","year":"2014","unstructured":"Guermazi, A. et al. Synovitis in knee osteoarthritis assessed by contrast-enhanced magnetic resonance imaging (MRI) is associated with radiographic tibiofemoral osteoarthritis and MRI-detected widespread cartilage damage: the MOST study. J. Rheumatol. 41, 501\u2013508 (2014).","journal-title":"J. Rheumatol."},{"key":"549_CR46","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1136\/ard.2010.131904","volume":"70","author":"E Yusuf","year":"2011","unstructured":"Yusuf, E., Kortekaas, M. C., Watt, I., Huizinga, T. W. & Kloppenburg, M. Do knee abnormalities visualised on MRI explain knee pain in knee osteoarthritis? A systematic review. Ann. Rheum. Dis. 70, 60\u201367 (2011).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR47","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.joca.2014.10.002","volume":"23","author":"X Wang","year":"2015","unstructured":"Wang, X., Hunter, D., Xu, J. & Ding, C. Metabolic triggered inflammation in osteoarthritis. Osteoarthr. Cartil. 23, 22\u201330 (2015).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR48","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1016\/j.joca.2009.03.006","volume":"17","author":"D Loeuille","year":"2009","unstructured":"Loeuille, D. et al. Magnetic resonance imaging in osteoarthritis: which method best reflects synovial membrane inflammation? Correlations with clinical, macroscopic and microscopic features. Osteoarthr. Cartil. 17, 1186\u20131192 (2009).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR49","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1002\/acr.22734","volume":"68","author":"AJ Kittelson","year":"2016","unstructured":"Kittelson, A. J., Stevens-Lapsley, J. E. & Schmiege, S. J. Determination of Pain Phenotypes in Knee Osteoarthritis: A Latent Class Analysis Using Data From the Osteoarthritis Initiative. Arthritis Care Res 68, 612\u2013620 (2016).","journal-title":"Arthritis Care Res"},{"key":"549_CR50","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.joca.2019.08.005","volume":"28","author":"FW Roemer","year":"2020","unstructured":"Roemer, F. W. et al. MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES). Osteoarthr. Cartil. 28, 71\u201381 (2020).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR51","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1016\/j.joca.2017.08.009","volume":"25","author":"LA Deveza","year":"2017","unstructured":"Deveza, L. A. et al. Knee osteoarthritis phenotypes and their relevance for outcomes: a systematic review. Osteoarthr. Cartil. 25, 1926\u20131941 (2017).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR52","doi-asserted-by":"publisher","first-page":"105","DOI":"10.2174\/1874325001812010105","volume":"12","author":"FRT Nelson","year":"2018","unstructured":"Nelson, F. R. T. The Value of Phenotypes in Knee Osteoarthritis Research. Open Orthop. J. 12, 105\u2013114 (2018).","journal-title":"Open Orthop. J."},{"key":"549_CR53","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s41927-025-00482-2","volume":"9","author":"G Gijon-Nogueron","year":"2025","unstructured":"Gijon-Nogueron, G. et al. Terminologies and definitions used to classify patients with osteoarthritis: a scoping review. BMC Rheumatol. 9, 32 (2025).","journal-title":"BMC Rheumatol."},{"key":"549_CR54","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1148\/radiol.2262012190","volume":"226","author":"TM Link","year":"2003","unstructured":"Link, T. M. et al. Osteoarthritis: MR imaging findings in different stages of disease and correlation with clinical findings. Radiology 226, 373\u2013381 (2003).","journal-title":"Radiology"},{"key":"549_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-020-03260-y","volume":"21","author":"M Vongsirinavarat","year":"2020","unstructured":"Vongsirinavarat, M., Nilmart, P., Somprasong, S. & Apinonkul, B. Identification of knee osteoarthritis disability phenotypes regarding activity limitation: a cluster analysis. BMC Musculoskelet. Disord. 21, 237 (2020).","journal-title":"BMC Musculoskelet. Disord."},{"key":"549_CR56","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1097\/j.pain.0000000000002856","volume":"164","author":"S Perrot","year":"2023","unstructured":"Perrot, S., Trouvin, A. P. & Bouhassira, D. Three dimensions of pain in osteoarthritis: development and validation of the Osteoarthritis Symptom Inventory Scale. Pain 164, 1566\u20131577 (2023).","journal-title":"Pain"},{"key":"549_CR57","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s00330-024-10928-9","volume":"35","author":"H Zhao","year":"2025","unstructured":"Zhao, H. et al. The value of deep learning-based X-ray techniques in detecting and classifying K-L grades of knee osteoarthritis: a systematic review and meta-analysis. Eur. Radio. 35, 327\u2013340 (2025).","journal-title":"Eur. Radio."},{"key":"549_CR58","doi-asserted-by":"publisher","first-page":"4015","DOI":"10.1007\/s00167-021-06768-5","volume":"30","author":"PY Joo","year":"2022","unstructured":"Joo, P. Y., Borjali, A., Chen, A. F., Muratoglu, O. K. & Varadarajan, K. M. Defining and predicting radiographic knee osteoarthritis progression: a systematic review of findings from the osteoarthritis initiative. Knee Surg. Sports Traumatol. Arthrosc. 30, 4015\u20134028 (2022).","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"549_CR59","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1007\/s11999-016-4732-4","volume":"474","author":"MD Kohn","year":"2016","unstructured":"Kohn, M. D., Sassoon, A. A. & Fernando, N. D. Classifications in Brief: Kellgren-Lawrence Classification of Osteoarthritis. Clin. Orthop. Relat. Res. 474, 1886\u20131893 (2016).","journal-title":"Clin. Orthop. Relat. Res."},{"key":"549_CR60","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/s41584-018-0010-z","volume":"14","author":"FW Roemer","year":"2018","unstructured":"Roemer, F. W., Kwoh, C. K., Hayashi, D., Felson, D. T. & Guermazi, A. The role of radiography and MRI for eligibility assessment in DMOAD trials of knee OA. Nat. Rev. Rheumatol. 14, 372\u2013380 (2018).","journal-title":"Nat. Rev. Rheumatol."},{"key":"549_CR61","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20132-7","volume":"8","author":"A Tiulpin","year":"2018","unstructured":"Tiulpin, A., Thevenot, J., Rahtu, E., Lehenkari, P. & Saarakkala, S. Automatic Knee Osteoarthritis Diagnosis from Plain Radiographs: A Deep Learning-Based Approach. Sci. Rep. 8, 1727 (2018).","journal-title":"Sci. Rep."},{"key":"549_CR62","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.joca.2024.10.009","volume":"33","author":"D Hayashi","year":"2025","unstructured":"Hayashi, D., Roemer, F. W. & Guermazi, A. Osteoarthritis year in review 2024: Imaging. Osteoarthr. Cartil. 33, 88\u201393 (2025).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR63","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1186\/s13018-024-05194-w","volume":"19","author":"Y Liu","year":"2024","unstructured":"Liu, Y. et al. Association of MRI-based knee osteoarthritis structural phenotypes with short-term structural progression and subsequent total knee replacement. J. Orthop. Surg. Res. 19, 699 (2024).","journal-title":"J. Orthop. Surg. Res."},{"key":"549_CR64","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1007\/s00256-022-04267-3","volume":"52","author":"D Hayashi","year":"2023","unstructured":"Hayashi, D., Roemer, F. W., Jarraya, M. & Guermazi, A. Update on recent developments in imaging of inflammation in osteoarthritis: a narrative review. Skelet. Radio. 52, 2057\u20132067 (2023).","journal-title":"Skelet. Radio."},{"key":"549_CR65","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1136\/annrheumdis-2014-205894","volume":"75","author":"I Atukorala","year":"2016","unstructured":"Atukorala, I. et al. Synovitis in knee osteoarthritis: a precursor of disease? Ann. Rheum. Dis. 75, 390\u2013395 (2016).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR66","doi-asserted-by":"crossref","unstructured":"Xuan, A. et al. The application of machine learning in early diagnosis of osteoarthritis: a narrative review. Ther. Adv. Musculoskelet. Dis. 15, 1759720x231158198 (2023).","DOI":"10.1177\/1759720X231158198"},{"key":"549_CR67","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1148\/radiol.212009","volume":"304","author":"J Li","year":"2022","unstructured":"Li, J. et al. MRI-bence. Radiology 304, 611\u2013621 (2022).","journal-title":"Radiology"},{"key":"549_CR68","doi-asserted-by":"crossref","unstructured":"Dang, Q. et al. MRI-based radiomics to determine the role of thigh muscle quality in the development of knee osteoarthritis: A discovery and validation study. J. Adv. Res. 79, 819\u2013831 (2025).","DOI":"10.1016\/j.jare.2025.04.013"},{"key":"549_CR69","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1136\/annrheumdis-2020-217160","volume":"80","author":"MA Bowes","year":"2021","unstructured":"Bowes, M. A. et al. Machine-learning, MRI bone shape and important clinical outcomes in osteoarthritis: data from the Osteoarthritis Initiative. Ann. Rheum. Dis. 80, 502\u2013508 (2021).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR70","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1136\/ard-2024-225872","volume":"84","author":"S Castagno","year":"2025","unstructured":"Castagno, S., Birch, M., van der Schaar, M. & McCaskie, A. Predicting rapid progression in knee osteoarthritis: a novel and interpretable automated machine learning approach, with specific focus on young patients and early disease. Ann. Rheum. Dis. 84, 124\u2013135 (2025).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR71","doi-asserted-by":"publisher","DOI":"10.1016\/j.artmed.2025.103138","volume":"167","author":"N Belton","year":"2025","unstructured":"Belton, N., Lawlor, A. & Curran, K. M. An AI system for continuous knee osteoarthritis severity grading: An anomaly detection inspired approach with few labels. Artif. Intell. Med. 167, 103138 (2025).","journal-title":"Artif. Intell. Med."},{"key":"549_CR72","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/s41746-025-01878-7","volume":"8","author":"SY Park","year":"2025","unstructured":"Park, S. Y. et al. Osteoarthritis progression pattern based on patient specific characteristics using machine learning. NPJ Digit. Med. 8, 464 (2025).","journal-title":"NPJ Digit. Med."},{"key":"549_CR73","first-page":"116","volume":"47","author":"A Fazio","year":"2024","unstructured":"Fazio, A. et al. The involvement of signaling pathways in the pathogenesis of osteoarthritis: An update. J. Orthop. Transl. 47, 116\u2013124 (2024).","journal-title":"J. Orthop. Transl."},{"key":"549_CR74","doi-asserted-by":"crossref","unstructured":"Molnar, V. et al. Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis. Int. J. Mol. Sci. 22, 9208 (2021).","DOI":"10.3390\/ijms22179208"},{"key":"549_CR75","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41368-018-0016-z","volume":"10","author":"T Hui","year":"2018","unstructured":"Hui, T. et al. Activation of \u03b2-catenin signaling in aggrecan-expressing cells in temporomandibular joint causes osteoarthritis-like defects. Int J. Oral. Sci. 10, 13 (2018).","journal-title":"Int J. Oral. Sci."},{"key":"549_CR76","doi-asserted-by":"publisher","first-page":"18535","DOI":"10.1002\/jcp.28491","volume":"234","author":"C Xia","year":"2019","unstructured":"Xia, C. et al. Activation of \u03b2-catenin in Col2-expressing chondrocytes leads to osteoarthritis-like defects in hip joint. J. Cell Physiol. 234, 18535\u201318543 (2019).","journal-title":"J. Cell Physiol."},{"key":"549_CR77","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41413-023-00253-0","volume":"11","author":"K Lu","year":"2023","unstructured":"Lu, K. et al. Upregulation of \u03b2-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain. Bone Res 11, 18 (2023).","journal-title":"Bone Res"},{"key":"549_CR78","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.joca.2020.02.027","volume":"28","author":"K Sun","year":"2020","unstructured":"Sun, K. et al. The PI3K\/AKT\/mTOR signaling pathway in osteoarthritis: a narrative review. Osteoarthr. Cartil. 28, 400\u2013409 (2020).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR79","first-page":"175","volume":"5","author":"W Qin","year":"2024","unstructured":"Qin, W. et al. Microarray analysis of signalling interactions between inflammation and angiogenesis in subchondral bone in temporomandibular joint osteoarthritis. Biomater. Transl. 5, 175\u2013184 (2024).","journal-title":"Biomater. Transl."},{"key":"549_CR80","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41413-022-00239-4","volume":"11","author":"X Du","year":"2023","unstructured":"Du, X., Cai, L., Xie, J. & Zhou, X. The role of TGF-beta3 in cartilage development and osteoarthritis. Bone Res. 11, 2 (2023).","journal-title":"Bone Res."},{"key":"549_CR81","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-018-1955-4","volume":"19","author":"G Ren","year":"2018","unstructured":"Ren, G. et al. Serum and synovial fluid cytokine profiling in hip osteoarthritis: distinct from knee osteoarthritis and correlated with pain. BMC Musculoskelet. Disord. 19, 39 (2018).","journal-title":"BMC Musculoskelet. Disord."},{"key":"549_CR82","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1002\/art.41161","volume":"72","author":"H Labinsky","year":"2020","unstructured":"Labinsky, H. et al. Multiparameter Analysis Identifies Heterogeneity in Knee Osteoarthritis Synovial Responses. Arthritis Rheumatol. 72, 598\u2013608 (2020).","journal-title":"Arthritis Rheumatol."},{"key":"549_CR83","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.3390\/jcm8101631","volume":"8","author":"R Grieshaber-Bouyer","year":"2019","unstructured":"Grieshaber-Bouyer, R. et al. Divergent mononuclear cell participation and cytokine release profiles define hip and knee osteoarthritis. J. Clin. Med. 8, 1631 (2019).","journal-title":"J. Clin. Med."},{"key":"549_CR84","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1136\/ard-2022-222773","volume":"82","author":"AJ Knights","year":"2023","unstructured":"Knights, A. J. et al. Synovial fibroblasts assume distinct functional identities and secrete R-spondin 2 in osteoarthritis. Ann. Rheum. Dis. 82, 272\u2013282 (2023).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR85","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67446-z","volume":"10","author":"MJ Peffers","year":"2020","unstructured":"Peffers, M. J. et al. SnoRNA signatures in cartilage ageing and osteoarthritis. Sci. Rep. 10, 10641 (2020).","journal-title":"Sci. Rep."},{"key":"549_CR86","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1097\/BOR.0000000000000567","volume":"31","author":"A Mobasheri","year":"2019","unstructured":"Mobasheri, A. et al. Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development: biochemical markers associated with emerging clinical phenotypes and molecular endotypes. Curr. Opin. Rheumatol. 31, 80\u201389 (2019).","journal-title":"Curr. Opin. Rheumatol."},{"key":"549_CR87","doi-asserted-by":"crossref","unstructured":"Rousseau, J. C., Chapurlat, R. & Garnero, P. Soluble biological markers in osteoarthritis. Ther. Adv. Musculoskelet. Dis. 13, 1759720x211040300 (2021).","DOI":"10.1177\/1759720X211040300"},{"key":"549_CR88","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1111\/os.14370","volume":"17","author":"H Li","year":"2025","unstructured":"Li, H. et al. Comprehensive analysis reveals the potential diagnostic value of biomarkers associated with aging and circadian rhythm in knee Osteoarthritis. Orthop. Surg. 17, 922\u2013938 (2025).","journal-title":"Orthop. Surg."},{"key":"549_CR89","doi-asserted-by":"crossref","unstructured":"Li, Y. et al. The application of extracellular vesicles in orthopedic diseases. Interdiscip. Med. 2, e20230055 (2024).","DOI":"10.1002\/INMD.20230055"},{"key":"549_CR90","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.joca.2024.10.003","volume":"33","author":"HD Welhaven","year":"2025","unstructured":"Welhaven, H. D., Welfley, A. H. & June, R. K. Osteoarthritis Year in Review 2024: Molecular biomarkers of osteoarthritis. Osteoarthr. Cartil. 33, 67\u201387 (2025).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR91","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1093\/rheumatology\/keaa693","volume":"60","author":"S Werdyani","year":"2021","unstructured":"Werdyani, S. et al. Endotypes of primary osteoarthritis identified by plasma metabolomics analysis. Rheumatology 60, 2735\u20132744 (2021).","journal-title":"Rheumatology"},{"key":"549_CR92","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.725568","volume":"9","author":"Z Lv","year":"2021","unstructured":"Lv, Z. et al. Molecular classification of knee Osteoarthritis. Front. Cell Dev. Biol. 9, 725568 (2021).","journal-title":"Front. Cell Dev. Biol."},{"key":"549_CR93","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/nrrheum.2016.209","volume":"13","author":"V Abella","year":"2017","unstructured":"Abella, V. et al. Leptin in the interplay of inflammation, metabolism and immune system disorders. Nat. Rev. Rheumatol. 13, 100\u2013109 (2017).","journal-title":"Nat. Rev. Rheumatol."},{"key":"549_CR94","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.biochi.2024.09.015","volume":"227","author":"N Zapata-Linares","year":"2024","unstructured":"Zapata-Linares, N. et al. Systemic and joint adipose tissue lipids and their role in osteoarthritis. Biochimie 227, 130\u2013138 (2024).","journal-title":"Biochimie"},{"key":"549_CR95","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-85945-9","volume":"15","author":"W Chen","year":"2025","unstructured":"Chen, W. et al. Identification of biomarkers for knee osteoarthritis through clinical data and machine learning models. Sci. Rep. 15, 1703 (2025).","journal-title":"Sci. Rep."},{"key":"549_CR96","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1136\/annrheumdis-2021-221763","volume":"81","author":"F Angelini","year":"2022","unstructured":"Angelini, F. et al. Osteoarthritis endotype discovery via clustering of biochemical marker data. Ann. Rheum. Dis. 81, 666\u2013675 (2022).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR97","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46663-4","volume":"15","author":"RL Nielsen","year":"2024","unstructured":"Nielsen, R. L. et al. Data-driven identification of predictive risk biomarkers for subgroups of osteoarthritis using interpretable machine learning. Nat. Commun. 15, 2817 (2024).","journal-title":"Nat. Commun."},{"key":"549_CR98","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.joca.2016.12.016","volume":"25","author":"A Mobasheri","year":"2017","unstructured":"Mobasheri, A., Bay-Jensen, A. C., van Spil, W. E., Larkin, J. & Levesque, M. C. Osteoarthritis Year in Review 2016: biomarkers (biochemical markers). Osteoarthr. Cartil. 25, 199\u2013208 (2017).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR99","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-016-1286-2","volume":"17","author":"A Dell\u2019Isola","year":"2016","unstructured":"Dell\u2019Isola, A., Allan, R., Smith, S. L., Marreiros, S. S. & Steultjens, M. Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature. BMC Musculoskelet. Disord. 17, 425 (2016).","journal-title":"BMC Musculoskelet. Disord."},{"key":"549_CR100","doi-asserted-by":"publisher","first-page":"e0191045","DOI":"10.1371\/journal.pone.0191045","volume":"13","author":"A Dell\u2019Isola","year":"2018","unstructured":"Dell\u2019Isola, A. & Steultjens, M. Classification of patients with knee osteoarthritis in clinical phenotypes: Data from the osteoarthritis initiative. PLoS One 13, e0191045 (2018).","journal-title":"PLoS One"},{"key":"549_CR101","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1002\/rai2.12018","volume":"01","author":"Y Cao","year":"2021","unstructured":"Cao, Y., Tang, S. A. & Ding, C. Inflammatory phenotype of osteoarthritis and its potential therapies. Rheumatol. Autoimmun. 01, 92\u2013100 (2021).","journal-title":"Rheumatol. Autoimmun."},{"key":"549_CR102","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101101","volume":"26","author":"Y Zhang","year":"2024","unstructured":"Zhang, Y., Gao, Z., Yang, X., Xu, Q. & Lu, Y. Leveraging high-throughput screening technologies in targeted mRNA delivery. Mater. Today Bio 26, 101101 (2024).","journal-title":"Mater. Today Bio"},{"key":"549_CR103","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1136\/ard-2023-224420","volume":"83","author":"Y Fan","year":"2024","unstructured":"Fan, Y. et al. Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration. Ann. Rheum. Dis. 83, 926\u2013944 (2024).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR104","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41413-020-00109-x","volume":"8","author":"C Yuan","year":"2020","unstructured":"Yuan, C. et al. Classification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas. Bone Res. 8, 38 (2020).","journal-title":"Bone Res."},{"key":"549_CR105","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1093\/rheumatology\/keaa391","volume":"60","author":"R Coutinho de Almeida","year":"2021","unstructured":"Coutinho de Almeida, R. et al. Identification and characterization of two consistent osteoarthritis subtypes by transcriptome and clinical data integration. Rheumatology 60, 1166\u20131175 (2021).","journal-title":"Rheumatology"},{"key":"549_CR106","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1136\/annrheumdis-2020-219760","volume":"80","author":"J Steinberg","year":"2021","unstructured":"Steinberg, J. et al. Linking chondrocyte and synovial transcriptional profile to clinical phenotype in osteoarthritis. Ann. Rheum. Dis. 80, 1070\u20131074 (2021).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR107","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1302\/2046-3758.1212.BJR-2023-0021.R2","volume":"12","author":"Y Xue","year":"2023","unstructured":"Xue, Y., Zhou, L. & Wang, J. Classification of distinct osteoarthritis subtypes with different knee joint tissues by gene expression profiles. Bone Jt. Res. 12, 702\u2013711 (2023).","journal-title":"Bone Jt. Res."},{"key":"549_CR108","doi-asserted-by":"publisher","first-page":"3875","DOI":"10.1007\/s10067-020-05106-3","volume":"39","author":"MKJ Jaggard","year":"2020","unstructured":"Jaggard, M. K. J. et al. Can metabolic profiling provide a new description of osteoarthritis and enable a personalised medicine approach? Clin. Rheumatol. 39, 3875\u20133882 (2020).","journal-title":"Clin. Rheumatol."},{"key":"549_CR109","doi-asserted-by":"publisher","first-page":"e0199618","DOI":"10.1371\/journal.pone.0199618","volume":"13","author":"JS Rockel","year":"2018","unstructured":"Rockel, J. S. et al. A classification modeling approach for determining metabolite signatures in osteoarthritis. PLoS One 13, e0199618 (2018).","journal-title":"PLoS One"},{"key":"549_CR110","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1016\/j.joca.2019.04.007","volume":"27","author":"AK Carlson","year":"2019","unstructured":"Carlson, A. K. et al. Characterization of synovial fluid metabolomic phenotypes of cartilage morphological changes associated with osteoarthritis. Osteoarthr. Cartil. 27, 1174\u20131184 (2019).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR111","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocarto.2021.100219","volume":"3","author":"B Rocha","year":"2021","unstructured":"Rocha, B. et al. Targeted phospholipidomic analysis of synovial fluid as a tool for osteoarthritis deep phenotyping. Osteoarthr. Cartil. Open 3, 100219 (2021).","journal-title":"Osteoarthr. Cartil. Open"},{"key":"549_CR112","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1001\/jama.2023.19675","volume":"330","author":"V Duong","year":"2023","unstructured":"Duong, V., Oo, W. M., Ding, C., Culvenor, A. G. & Hunter, D. J. Evaluation and treatment of knee pain: a review. JAMA 330, 1568\u20131580 (2023).","journal-title":"JAMA"},{"key":"549_CR113","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","volume":"393","author":"DJ Hunter","year":"2019","unstructured":"Hunter, D. J. & Bierma-Zeinstra, S. Osteoarthritis. Lancet 393, 1745\u20131759 (2019).","journal-title":"Lancet"},{"key":"549_CR114","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","volume":"27","author":"RR Bannuru","year":"2019","unstructured":"Bannuru, R. R. et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr. Cartil. 27, 1578\u20131589 (2019).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR115","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocarto.2024.100438","volume":"6","author":"S Espinosa-Salas","year":"2024","unstructured":"Espinosa-Salas, S., Bagherzadeh, L., Wafford, Q. E., Witte, G. & Schnitzer, T. J. Does sex affect the efficacy of systemic pharmacological treatments of pain in knee osteoarthritis? A systematic review. Osteoarthr. Cartil. Open 6, 100438 (2024).","journal-title":"Osteoarthr. Cartil. Open"},{"key":"549_CR116","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-020-03363-6","volume":"21","author":"AO Masson","year":"2020","unstructured":"Masson, A. O. & Krawetz, R. J. Understanding cartilage protection in OA and injury: a spectrum of possibilities. BMC Musculoskelet. Disord. 21, 432 (2020).","journal-title":"BMC Musculoskelet. Disord."},{"key":"549_CR117","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.joca.2013.10.018","volume":"22","author":"MA Karsdal","year":"2014","unstructured":"Karsdal, M. A. et al. Osteoarthritis-a case for personalized health care? Osteoarthr. Cartil. 22, 7\u201316 (2014).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR118","doi-asserted-by":"publisher","first-page":"n2321","DOI":"10.1136\/bmj.n2321","volume":"375","author":"BR da Costa","year":"2021","unstructured":"da Costa, B. R. et al. Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis. Bmj 375, n2321 (2021).","journal-title":"Bmj"},{"key":"549_CR119","first-page":"CD004257","volume":"2006","author":"T Towheed","year":"2006","unstructured":"Towheed, T. et al. Acetaminophen for osteoarthritis. Cochrane Database Syst. Rev. 2006, CD004257 (2006).","journal-title":"Cochrane Database Syst. Rev."},{"key":"549_CR120","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/j.joca.2011.04.013","volume":"19","author":"SP Verkleij","year":"2011","unstructured":"Verkleij, S. P., Luijsterburg, P. A., Bohnen, A. M., Koes, B. W. & Bierma-Zeinstra, S. M. NSAIDs vs acetaminophen in knee and hip osteoarthritis: a systematic review regarding heterogeneity influencing the outcomes. Osteoarthr. Cartil. 19, 921\u2013929 (2011).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR121","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1136\/ard.2005.040519","volume":"65","author":"O Svensson","year":"2006","unstructured":"Svensson, O., Malmen\u00e4s, M., Fajutrao, L., Roos, E. M. & Lohmander, L. S. Greater reduction of knee than hip pain in osteoarthritis treated with naproxen, as evaluated by WOMAC and SF-36. Ann. Rheum. Dis. 65, 781\u2013784 (2006).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR122","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1007\/s00296-024-05678-2","volume":"44","author":"H Fang","year":"2024","unstructured":"Fang, H. et al. The relationship between MRI-detected hip abnormalities and hip pain in hip osteoarthritis: a systematic review. Rheumatol. Int. 44, 1887\u20131896 (2024).","journal-title":"Rheumatol. Int."},{"key":"549_CR123","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.bone.2012.02.012","volume":"51","author":"CR Scanzello","year":"2012","unstructured":"Scanzello, C. R. & Goldring, S. R. The role of synovitis in osteoarthritis pathogenesis. Bone 51, 249\u2013257 (2012).","journal-title":"Bone"},{"key":"549_CR124","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.1172\/JCI118717","volume":"97","author":"GD Anderson","year":"1996","unstructured":"Anderson, G. D. et al. Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis. J. Clin. Invest 97, 2672\u20132679 (1996).","journal-title":"J. Clin. Invest"},{"key":"549_CR125","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1001\/jama.1951.03670340019005","volume":"147","author":"JL Hollander","year":"1951","unstructured":"Hollander, J. L., Brown, E. M. Jr, Jessar, R. A. & Brown, C. Y. Hydrocortisone and cortisone injected into arthritic joints; comparative effects of and use of hydrocortisone as a local antiarthritic agent. J. Am. Med Assoc. 147, 1629\u20131635 (1951).","journal-title":"J. Am. Med Assoc."},{"key":"549_CR126","doi-asserted-by":"publisher","first-page":"e003030","DOI":"10.1136\/rmdopen-2023-003030","volume":"9","author":"A D\u00f8ssing","year":"2023","unstructured":"D\u00f8ssing, A. et al. Comparative effectiveness of pharmacological interventions for hand osteoarthritis: a systematic review and network meta-analysis of randomised trials. RMD Open 9, e003030 (2023).","journal-title":"RMD Open"},{"key":"549_CR127","doi-asserted-by":"publisher","DOI":"10.1016\/j.ostima.2023.100163","volume":"3","author":"A Guermazi","year":"2023","unstructured":"Guermazi, A., Hunter, D. J. & Kloppenburg, M. Debate: Intra-articular steroid injections for osteoarthritis - harmful or helpful?(\u2730,\u2730\u2730). Osteoarthr. Imaging 3, 100163 (2023).","journal-title":"Osteoarthr. Imaging"},{"key":"549_CR128","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2024.115300","volume":"208","author":"FA Chapa-Villarreal","year":"2024","unstructured":"Chapa-Villarreal, F. A., Stephens, M., Pavlicin, R., Beussman, M. & Peppas, N. A. Therapeutic delivery systems for rheumatoid arthritis based on hydrogel carriers. Adv. Drug Deliv. Rev. 208, 115300 (2024).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"549_CR129","doi-asserted-by":"publisher","first-page":"3958","DOI":"10.3390\/jcm11143958","volume":"11","author":"Y Li","year":"2022","unstructured":"Li, Y. et al. Relative Efficacy and Safety of Anti-Inflammatory Biologic Agents for Osteoarthritis: A Conventional and Network Meta-Analysis. J. Clin. Med 11, 3958 (2022).","journal-title":"J. Clin. Med"},{"key":"549_CR130","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1136\/ard.2006.053272","volume":"65","author":"M Grunke","year":"2006","unstructured":"Grunke, M. & Schulze-Koops, H. Successful treatment of inflammatory knee osteoarthritis with tumour necrosis factor blockade. Ann. Rheum. Dis. 65, 555\u2013556 (2006).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR131","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1136\/ard.2011.149849","volume":"71","author":"G Verbruggen","year":"2012","unstructured":"Verbruggen, G., Wittoek, R., Vander Cruyssen, B. & Elewaut, D. Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification. Ann. Rheum. Dis. 71, 891\u2013898 (2012).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR132","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1136\/annrheumdis-2018-213202","volume":"77","author":"M Kloppenburg","year":"2018","unstructured":"Kloppenburg, M. et al. Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial. Ann. Rheum. Dis. 77, 1757\u20131764 (2018).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR133","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1093\/rheumatology\/key016","volume":"57","author":"M Loef","year":"2018","unstructured":"Loef, M. et al. TNF inhibitor treatment is associated with a lower risk of hand osteoarthritis progression in rheumatoid arthritis patients after 10 years. Rheumatology 57, 1917\u20131924 (2018).","journal-title":"Rheumatology"},{"key":"549_CR134","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/nrrheum.2016.166","volume":"12","author":"G Schett","year":"2016","unstructured":"Schett, G., Dayer, J. M. & Manger, B. Interleukin-1 function and role in rheumatic disease. Nat. Rev. Rheumatol. 12, 14\u201324 (2016).","journal-title":"Nat. Rev. Rheumatol."},{"key":"549_CR135","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41434-025-00515-y","volume":"32","author":"K Zhou","year":"2025","unstructured":"Zhou, K. et al. Co-delivery of IL-1Ra and SOX9 via AAV inhibits inflammation and promotes cartilage repair in surgically induced osteoarthritis animal models. Gene Ther. 32, 211\u2013222 (2025).","journal-title":"Gene Ther."},{"key":"549_CR136","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1002\/art.40840","volume":"71","author":"RM Fleischmann","year":"2019","unstructured":"Fleischmann, R. M. et al. A Phase II Trial of Lutikizumab, an Anti-Interleukin-1\u03b1\/\u03b2 dual variable domain immunoglobulin, in knee osteoarthritis patients with Synovitis. Arthritis Rheumatol. 71, 1056\u20131069 (2019).","journal-title":"Arthritis Rheumatol."},{"key":"549_CR137","doi-asserted-by":"publisher","DOI":"10.1186\/ar3430","volume":"13","author":"SB Cohen","year":"2011","unstructured":"Cohen, S. B. et al. A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee. Arthritis Res. Ther. 13, R125 (2011).","journal-title":"Arthritis Res. Ther."},{"key":"549_CR138","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1080\/14728214.2024.2386174","volume":"29","author":"L Pan","year":"2024","unstructured":"Pan, L., Nagib, L., Ganguly, S., Moorthy, A. & Tahir, H. A comprehensive review of phase 2\/3 trials in osteoarthritis: an expert opinion. Expert Opin. Emerg. Drugs 29, 347\u2013359 (2024).","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"549_CR139","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1016\/S0140-6736(23)01572-6","volume":"402","author":"Y Wang","year":"2023","unstructured":"Wang, Y. et al. Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial. Lancet 402, 1764\u20131772 (2023).","journal-title":"Lancet"},{"key":"549_CR140","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.7326\/M24-0303","volume":"177","author":"SR Kingsbury","year":"2024","unstructured":"Kingsbury, S. R. et al. Pain Reduction With Oral Methotrexate in Knee Osteoarthritis : A Randomized, Placebo-Controlled Clinical Trial. Ann. Intern. Med. 177, 1145\u20131156 (2024).","journal-title":"Ann. Intern. Med."},{"key":"549_CR141","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1001\/jamainternmed.2025.1359","volume":"185","author":"Z Zhu","year":"2025","unstructured":"Zhu, Z. et al. Low-Dose Methotrexate for the treatment of inflammatory knee osteoarthritis: a randomized clinical trial. JAMA Intern Med 185, 808\u2013816 (2025).","journal-title":"JAMA Intern Med"},{"key":"549_CR142","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1002\/msc.1538","volume":"19","author":"F Raposo","year":"2021","unstructured":"Raposo, F., Ramos, M. & L\u00facia Cruz, A. Effects of exercise on knee osteoarthritis: A systematic review. Musculoskelet. Care 19, 399\u2013435 (2021).","journal-title":"Musculoskelet. Care"},{"key":"549_CR143","doi-asserted-by":"publisher","DOI":"10.1177\/23259671231172773","volume":"11","author":"L Mo","year":"2023","unstructured":"Mo, L., Jiang, B., Mei, T. & Zhou, D. Exercise therapy for knee osteoarthritis: a systematic review and network meta-analysis. Orthop. J. Sports Med. 11, 23259671231172773 (2023).","journal-title":"Orthop. J. Sports Med."},{"key":"549_CR144","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1002\/art.42241","volume":"74","author":"GH Lo","year":"2022","unstructured":"Lo, G. H. et al. Association Between Walking for Exercise and Symptomatic and Structural Progression in Individuals With Knee Osteoarthritis: Data From the Osteoarthritis Initiative Cohort. Arthritis Rheumatology 74, 1660\u20131667 (2022).","journal-title":"Arthritis Rheumatology"},{"key":"549_CR145","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1136\/annrheumdis-2012-201691","volume":"72","author":"DA Dor\u00e9","year":"2013","unstructured":"Dor\u00e9, D. A. et al. The association between objectively measured physical activity and knee structural change using MRI. Ann. Rheum. Dis. 72, 1170\u20131175 (2013).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR146","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.ard.2025.01.019","volume":"84","author":"H He","year":"2025","unstructured":"He, H. et al. Association of walking with incident knee osteoarthritis: a prospective cohort study using data from the UK Biobank. Ann. Rheum. Dis. 84, 632\u2013642 (2025).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR147","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1136\/ard-2023-223845","volume":"82","author":"H Zhu","year":"2023","unstructured":"Zhu, H. et al. Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort. Ann. Rheum. Dis. 82, 1218\u20131226 (2023).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR148","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s12950-019-0218-y","volume":"16","author":"Q Que","year":"2019","unstructured":"Que, Q. et al. The GLP-1 agonist, liraglutide, ameliorates inflammation through the activation of the PKA\/CREB pathway in a rat model of knee osteoarthritis. J. Inflammation 16, 13 (2019).","journal-title":"J. Inflammation"},{"key":"549_CR149","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0217-y","volume":"9","author":"J Chen","year":"2018","unstructured":"Chen, J. et al. Glucagon-like peptide-1 receptor regulates endoplasmic reticulum stress-induced apoptosis and the associated inflammatory response in chondrocytes and the progression of osteoarthritis in rat. Cell Death Dis. 9, 212 (2018).","journal-title":"Cell Death Dis."},{"key":"549_CR150","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1056\/NEJMoa2403664","volume":"391","author":"H Bliddal","year":"2024","unstructured":"Bliddal, H. et al. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. N. Engl. J. Med. 391, 1573\u20131583 (2024).","journal-title":"N. Engl. J. Med."},{"key":"549_CR151","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.3390\/diagnostics14242829","volume":"14","author":"SP Osei","year":"2024","unstructured":"Osei, S. P. et al. Gastrointestinal Safety Assessment of GLP-1 receptor agonists in the us: a real-world adverse events analysis from the FAERS Database. Diagnostics 14, 2829 (2024).","journal-title":"Diagnostics"},{"key":"549_CR152","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/s41366-024-01653-w","volume":"49","author":"Z Salis","year":"2025","unstructured":"Salis, Z., Gallagher, R., Lawler, L. & Sainsbury, A. Loss of body weight is dose-dependently associated with reductions in symptoms of hip osteoarthritis. Int J. Obesity 49, 147\u2013153 (2025).","journal-title":"Int J. Obesity"},{"key":"549_CR153","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/BF02982710","volume":"12","author":"SL Miller","year":"2008","unstructured":"Miller, S. L. & Wolfe, R. R. The danger of weight loss in the elderly. J. Nutr. Health Aging 12, 487\u2013491 (2008).","journal-title":"J. Nutr. Health Aging"},{"key":"549_CR154","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.952560","volume":"13","author":"Y Song","year":"2022","unstructured":"Song, Y., Wu, Z. & Zhao, P. The effects of metformin in the treatment of osteoarthritis: Current perspectives. Front. Pharmacol. 13, 952560 (2022).","journal-title":"Front. Pharmacol."},{"key":"549_CR155","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1093\/rheumatology\/keac467","volume":"62","author":"D Li","year":"2023","unstructured":"Li, D. et al. Metformin attenuates osteoarthritis by targeting chondrocytes, synovial macrophages and adipocytes. Rheumatolgy 62, 1652\u20131661 (2023).","journal-title":"Rheumatolgy"},{"key":"549_CR156","doi-asserted-by":"publisher","first-page":"e233646","DOI":"10.1001\/jamanetworkopen.2023.3646","volume":"6","author":"MC Baker","year":"2023","unstructured":"Baker, M. C. et al. Development of Osteoarthritis in Adults With Type 2 Diabetes Treated With Metformin vs a Sulfonylurea. JAMA Netw. Open 6, e233646 (2023).","journal-title":"JAMA Netw. Open"},{"key":"549_CR157","doi-asserted-by":"publisher","first-page":"2858","DOI":"10.3390\/biomedicines11102858","volume":"11","author":"A Bernetti","year":"2023","unstructured":"Bernetti, A. et al. Could hyaluronic acid be considered as a senomorphic agent in knee osteoarthritis? A Syst Rev. Biomedicines 11, 2858 (2023).","journal-title":"Biomedicines"},{"key":"549_CR158","first-page":"111","volume":"50","author":"J Lu","year":"2025","unstructured":"Lu, J., Gao, Z., He, W. & Lu, Y. Harnessing the potential of hyaluronic acid methacrylate (HAMA) hydrogel for clinical applications in orthopaedic diseases. J. Orthop. Transl. 50, 111\u2013128 (2025).","journal-title":"J. Orthop. Transl."},{"key":"549_CR159","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-023-06925-6","volume":"24","author":"X Qiao","year":"2023","unstructured":"Qiao, X. et al. Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis. BMC Musculoskelet. Disord. 24, 926 (2023).","journal-title":"BMC Musculoskelet. Disord."},{"key":"549_CR160","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1136\/ard.2008.094623","volume":"69","author":"X Chevalier","year":"2010","unstructured":"Chevalier, X. et al. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann. Rheum. Dis. 69, 113\u2013119 (2010).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR161","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.joca.2005.09.003","volume":"14","author":"M Kirchner","year":"2006","unstructured":"Kirchner, M. & Marshall, D. A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee. Osteoarthr. Cartil. 14, 154\u2013162 (2006).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR162","doi-asserted-by":"publisher","first-page":"S36","DOI":"10.1016\/j.arth.2023.03.079","volume":"38","author":"AA Habibi","year":"2023","unstructured":"Habibi, A. A. et al. Patient-Reported Outcomes Following Intra-articular Hyaluronic Acid for Knee Osteoarthritis. J. Arthroplast. 38, S36\u2013s41 (2023).","journal-title":"J. Arthroplast."},{"key":"549_CR163","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1002\/art.24301","volume":"60","author":"P Richette","year":"2009","unstructured":"Richette, P. et al. Effect of hyaluronic acid in symptomatic hip osteoarthritis: a multicenter, randomized, placebo-controlled trial. Arthritis Rheum. 60, 824\u2013830 (2009).","journal-title":"Arthritis Rheum."},{"key":"549_CR164","doi-asserted-by":"publisher","first-page":"1619s","DOI":"10.1177\/19476035211017320","volume":"13","author":"D Webner","year":"2021","unstructured":"Webner, D., Huang, Y. & Hummer, C. D. 3rd. Intraarticular Hyaluronic Acid Preparations for Knee Osteoarthritis: Are Some Better Than Others? Cartilage 13, 1619s\u20131636s (2021).","journal-title":"Cartilage"},{"key":"549_CR165","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1186\/s13018-023-04119-3","volume":"18","author":"Z Wang","year":"2023","unstructured":"Wang, Z., Zhu, P., Liao, B., You, H. & Cai, Y. Effects and action mechanisms of individual cytokines contained in PRP on osteoarthritis. J. Orthop. Surg. Res 18, 713 (2023).","journal-title":"J. Orthop. Surg. Res"},{"key":"549_CR166","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1001\/jama.2021.19415","volume":"326","author":"KL Bennell","year":"2021","unstructured":"Bennell, K. L. et al. Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial. JAMA 326, 2021\u20132030 (2021).","journal-title":"JAMA"},{"key":"549_CR167","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/s00167-016-4110-5","volume":"25","author":"TM Duymus","year":"2017","unstructured":"Duymus, T. M. et al. Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options. Knee Surg. Sports Traumatol. Arthrosc. 25, 485\u2013492 (2017).","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"549_CR168","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1177\/0363546518814532","volume":"47","author":"A Di Martino","year":"2019","unstructured":"Di Martino, A. et al. Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial. Am. J. Sports Med 47, 347\u2013354 (2019).","journal-title":"Am. J. Sports Med"},{"key":"549_CR169","first-page":"444","volume":"19","author":"Y Cai","year":"2023","unstructured":"Cai, Y. et al. Enhanced osteoarthrierapy by nanoengineered mesenchymal stem cells using biomimetic CuS nanoparticles loaded with plasmid DNA encoding TGF-\u03b21. Bioact. Mater. 19, 444\u2013457 (2023).","journal-title":"Bioact. Mater."},{"key":"549_CR170","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121474","volume":"283","author":"Y Lu","year":"2022","unstructured":"Lu, Y. et al. Highly effective rheumatoid arthritis therapy by peptide-promoted nanomodification of mesenchymal stem cells. Biomaterials 283, 121474 (2022).","journal-title":"Biomaterials"},{"key":"549_CR171","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.joca.2018.02.906","volume":"26","author":"DS Jevotovsky","year":"2018","unstructured":"Jevotovsky, D. S., Alfonso, A. R., Einhorn, T. A. & Chiu, E. S. Osteoarthritis and stem cell therapy in humans: a systematic review. Osteoarthr. Cartil. 26, 711\u2013729 (2018).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR172","doi-asserted-by":"publisher","first-page":"963689723122188","DOI":"10.1177\/09636897231221882","volume":"33","author":"CF Chen","year":"2024","unstructured":"Chen, C. F. et al. Safety and Tolerability of Intra-Articular Injection of Adipose-Derived Mesenchymal Stem Cells GXCPC1 in 11 Subjects With Knee Osteoarthritis: A Nonrandomized Pilot Study Without a Control Arm. Cell Transpl. 33, 9636897231221882 (2024).","journal-title":"Cell Transpl."},{"key":"549_CR173","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1007\/s00167-006-0124-8","volume":"14","author":"M Agung","year":"2006","unstructured":"Agung, M. et al. Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surg. Sports Traumatol. Arthrosc. 14, 1307\u20131314 (2006).","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"549_CR174","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1097\/PHM.0000000000001930","volume":"101","author":"D Miller","year":"2022","unstructured":"Miller, D. et al. Adipose-derived stem cells, obesity, and inflammation: a systematic review and implications for osteoarthritis treatment. Am. J. Phys. Med. Rehabil. 101, 879\u2013887 (2022).","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"549_CR175","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1001\/jama.2019.14735","volume":"322","author":"MC Hochberg","year":"2019","unstructured":"Hochberg, M. C. et al. Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial. Jama 322, 1360\u20131370 (2019).","journal-title":"Jama"},{"key":"549_CR176","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1356-8","volume":"15","author":"D Reker","year":"2017","unstructured":"Reker, D. et al. Sprifermin (rhFGF18) modulates extracellular matrix turnover in cartilage explants ex vivo. J. Transl. Med. 15, 250 (2017).","journal-title":"J. Transl. Med."},{"key":"549_CR177","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/j.joca.2013.02.165","volume":"21","author":"A Valsesia","year":"2013","unstructured":"Valsesia, A. et al. Exploratory biomarker analysis reveals a genetic epistatic interaction in interleukin 1 receptor antagonist (IL1RN) gene associated to cartilage volume growth measured by MRI in response to sprifermin therapy in patients with knee radiographic osteoarthritis. Osteoarthr. Cartil. 21, 1063\u20134584 (2013).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR178","first-page":"445","volume":"34","author":"LE Dahlberg","year":"2016","unstructured":"Dahlberg, L. E. et al. A first-in-human, double-blind, randomised, placebo-controlled, dose ascending study of intra-articular rhFGF18 (sprifermin) in patients with advanced knee osteoarthritis. Clin. Exp. Rheumatol. 34, 445\u2013450 (2016).","journal-title":"Clin. Exp. Rheumatol."},{"key":"549_CR179","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.786546","volume":"9","author":"Z Song","year":"2021","unstructured":"Song, Z. et al. Sprifermin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-Related Diseases. Front Cell Dev. Biol. 9, 786546 (2021).","journal-title":"Front Cell Dev. Biol."},{"key":"549_CR180","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1080\/03008207.2025.2490797","volume":"66","author":"K Takase","year":"2025","unstructured":"Takase, K., McCulloch, P. C., Yik, J. H. N. & Haudenschild, D. R. Clinical and molecular landscape of post-traumatic osteoarthritis. Connect Tissue Res. 66, 373\u2013379 (2025).","journal-title":"Connect Tissue Res."},{"key":"549_CR181","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2024.1401207","volume":"12","author":"M Gardashli","year":"2024","unstructured":"Gardashli, M. et al. Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review. Front Bioeng. Biotechnol. 12, 1401207 (2024).","journal-title":"Front Bioeng. Biotechnol."},{"key":"549_CR182","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1186\/s13075-022-02881-z","volume":"24","author":"G Dwivedi","year":"2022","unstructured":"Dwivedi, G. et al. Inflammatory cytokines and mechanical injury induce post-traumatic osteoarthritis-like changes in a human cartilage-bone-synovium microphysiological system. Arthritis Res. Ther. 24, 198 (2022).","journal-title":"Arthritis Res. Ther."},{"key":"549_CR183","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121944","volume":"329","author":"M Jim\u00e9nez-Muro","year":"2023","unstructured":"Jim\u00e9nez-Muro, M., Soriano-Roman\u00ed, L., Mora, G., Ricciardelli, D. & Nieto, J. A. The microbiota-metabolic syndrome axis as a promoter of metabolic osteoarthritis. Life Sci. 329, 121944 (2023).","journal-title":"Life Sci."},{"key":"549_CR184","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/s41584-024-01143-3","volume":"20","author":"M Binvignat","year":"2024","unstructured":"Binvignat, M., Sellam, J., Berenbaum, F. & Felson, D. T. The role of obesity and adipose tissue dysfunction in osteoarthritis pain. Nat. Rev. Rheumatol. 20, 565\u2013584 (2024).","journal-title":"Nat. Rev. Rheumatol."},{"key":"549_CR185","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72227-9","volume":"10","author":"CJ Alves","year":"2020","unstructured":"Alves, C. J. et al. Nociceptive mechanisms driving pain in a post-traumatic osteoarthritis mouse model. Sci. Rep. 10, 15271 (2020).","journal-title":"Sci. Rep."},{"key":"549_CR186","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/s41584-025-01234-9","volume":"21","author":"J Barroso","year":"2025","unstructured":"Barroso, J., Branco, P. & Apkarian, A. V. The causal role of brain circuits in osteoarthritis pain. Nat. Rev. Rheumatol. 21, 261\u2013274 (2025).","journal-title":"Nat. Rev. Rheumatol."},{"key":"549_CR187","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3390\/biologics5030027","volume":"5","author":"LJ Coleman","year":"2025","unstructured":"Coleman, L. J., Byrne, J. L., Edwards, S. & O\u2019Hara, R. Advancing Early Detection of Osteoarthritis Through Biomarker Profiling and Predictive Modelling: A Review. Biologics 5, 27 (2025).","journal-title":"Biologics"},{"key":"549_CR188","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.3390\/diagnostics14151660","volume":"14","author":"LJ Coleman","year":"2024","unstructured":"Coleman, L. J., Byrne, J. L., Edwards, S. & O\u2019Hara, R. Utilising Discriminant Function Analysis (DFA) for Classifying Osteoarthritis (OA) Patients and Volunteers Based on Biomarker Concentration. Diagnostics 14, 1660 (2024).","journal-title":"Diagnostics"},{"key":"549_CR189","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1002\/2211-5463.13613","volume":"13","author":"F Yu","year":"2023","unstructured":"Yu, F., Bai, H., Zhang, Z., Ma, T. & Gao, L. Combined detection of serum CTX-II and C2C in a rat model of ACLT-induced osteoarthritis. FEBS Open Bio 13, 1485\u20131494 (2023).","journal-title":"FEBS Open Bio"},{"key":"549_CR190","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s40122-024-00592-8","volume":"13","author":"V Sethi","year":"2024","unstructured":"Sethi, V., Anand, C. & Della Pasqua, O. Clinical assessment of osteoarthritis pain: contemporary scenario, challenges, and future perspectives. Pain. Ther. 13, 391\u2013408 (2024).","journal-title":"Pain. Ther."},{"key":"549_CR191","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/s41584-024-01126-4","volume":"20","author":"A Mobasheri","year":"2024","unstructured":"Mobasheri, A. & Loeser, R. Clinical phenotypes, molecular endotypes and theratypes in OA therapeutic development. Nat. Rev. Rheumatol. 20, 525\u2013526 (2024).","journal-title":"Nat. Rev. Rheumatol."},{"key":"549_CR192","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100587","volume":"29-30","author":"A Cui","year":"2020","unstructured":"Cui, A. et al. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. Eclinicalmedicine 29-30, 100587 (2020).","journal-title":"Eclinicalmedicine"},{"key":"549_CR193","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/art.40692","volume":"71","author":"D Misra","year":"2019","unstructured":"Misra, D. et al. Risk of knee osteoarthritis with obesity, sarcopenic obesity, and sarcopenia. Arthritis Rheumatol. 71, 232\u2013237 (2019).","journal-title":"Arthritis Rheumatol."},{"key":"549_CR194","doi-asserted-by":"publisher","first-page":"e248968","DOI":"10.1001\/jamanetworkopen.2024.8968","volume":"7","author":"Y Wu","year":"2024","unstructured":"Wu, Y. et al. Weight-bearing physical activity, lower-limb muscle mass, and risk of knee osteoarthritis. JAMA Netw. Open 7, e248968 (2024).","journal-title":"JAMA Netw. Open"},{"key":"549_CR195","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.rdc.2024.03.003","volume":"50","author":"WM Oo","year":"2024","unstructured":"Oo, W. M. Prospects of disease-modifying osteoarthritis drugs. Rheum. Dis. Clin. North Am. 50, 483\u2013518 (2024).","journal-title":"Rheum. Dis. Clin. North Am."},{"key":"549_CR196","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s40520-024-02714-w","volume":"36","author":"G Herrero-Beaumont","year":"2024","unstructured":"Herrero-Beaumont, G. et al. Systemic osteoarthritis: the difficulty of categorically naming a continuous condition. Aging Clin. Exp. Res. 36, 45 (2024).","journal-title":"Aging Clin. Exp. Res."},{"key":"549_CR197","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocarto.2024.100440","volume":"6","author":"HHT Li","year":"2024","unstructured":"Li, H. H. T., Chan, L. C., Chan, P. K. & Wen, C. An interpretable knee replacement risk assessment system for osteoarthritis patients. Osteoarthr. Cartil. Open 6, 100440 (2024).","journal-title":"Osteoarthr. Cartil. Open"},{"key":"549_CR198","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.joca.2014.12.019","volume":"23","author":"MA Karsdal","year":"2015","unstructured":"Karsdal, M. A. et al. Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials. Osteoarthr. Cartil. 23, 532\u2013543 (2015).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR199","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.joca.2021.10.008","volume":"30","author":"AC Bay-Jensen","year":"2022","unstructured":"Bay-Jensen, A. C. et al. Low levels of type II collagen formation (PRO-C2) are associated with response to sprifermin: a pre-defined, exploratory biomarker analysis from the FORWARD study. Osteoarthr. Cartil. 30, 92\u201399 (2022).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR200","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1002\/cpdd.1042","volume":"11","author":"E van der Aar","year":"2022","unstructured":"van der Aar, E. et al. Safety, Pharmacokinetics, and Pharmacodynamics of the ADAMTS-5 Inhibitor GLPG1972\/S201086 in Healthy Volunteers and Participants With Osteoarthritis of the Knee or Hip. Clin. Pharm. Drug Dev. 11, 112\u2013122 (2022).","journal-title":"Clin. Pharm. Drug Dev."},{"key":"549_CR201","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1136\/annrheumdis-2016-209252","volume":"76","author":"VB Kraus","year":"2017","unstructured":"Kraus, V. B. et al. Predictive validity of biochemical biomarkers in knee osteoarthritis: data from the FNIH OA Biomarkers Consortium. Ann. Rheum. Dis. 76, 186\u2013195 (2017).","journal-title":"Ann. Rheum. Dis."},{"key":"549_CR202","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1080\/14737159.2025.2550639","volume":"25","author":"CS Thudium","year":"2025","unstructured":"Thudium, C. S. et al. Diagnosing, treating and monitoring the inflammatory endotype in osteoarthritis clinical trials. Expert Rev. Mol. Diagn. 25, 709\u2013722 (2025).","journal-title":"Expert Rev. Mol. Diagn."},{"key":"549_CR203","doi-asserted-by":"publisher","first-page":"iv88","DOI":"10.1093\/rheumatology\/key062","volume":"57","author":"KS Dziedzic","year":"2018","unstructured":"Dziedzic, K. S. & Allen, K. D. Challenges and controversies of complex interventions in osteoarthritis management: recognizing inappropriate and discordant care. Rheumatology 57, iv88\u2013iv98 (2018).","journal-title":"Rheumatology"},{"key":"549_CR204","first-page":"100","volume":"45","author":"T Jiang","year":"2024","unstructured":"Jiang, T. et al. Radiomics signature of osteoarthritis: Current status and perspective. J. Orthop. Transl. 45, 100\u2013106 (2024).","journal-title":"J. Orthop. Transl."},{"key":"549_CR205","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/j.joca.2021.04.001","volume":"29","author":"M Wu","year":"2021","unstructured":"Wu, M. et al. Spectroscopic photoacoustic imaging of cartilage damage. Osteoarthr. Cartil. 29, 1071\u20131080 (2021).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR206","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1002\/art.42915","volume":"76","author":"S Li","year":"2024","unstructured":"Li, S. et al. Integrating radiomics and neural networks for knee osteoarthritis incidence prediction. Arthritis Rheumatol. 76, 1377\u20131386 (2024).","journal-title":"Arthritis Rheumatol."},{"key":"549_CR207","doi-asserted-by":"publisher","first-page":"e0316824","DOI":"10.1371\/journal.pone.0316824","volume":"20","author":"C Lu","year":"2025","unstructured":"Lu, C. et al. Mendelian randomization analysis to identify potential drug targets for osteoarthritis. PLoS One 20, e0316824 (2025).","journal-title":"PLoS One"},{"key":"549_CR208","doi-asserted-by":"publisher","DOI":"10.1016\/j.celbio.2025.100148","volume":"10","author":"Z Huang","year":"2025","unstructured":"Huang, Z. et al. Cuproptosis improves CAR-T cell therapy in osteosarcoma. Cell Biomater. 10, 100148 (2025).","journal-title":"Cell Biomater."},{"key":"549_CR209","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2025.100667","volume":"6","author":"L Zhou","year":"2025","unstructured":"Zhou, L. et al. Organoids and organs-on-chips: Recent advances, applications in drug development, and regulatory challenges. Med 6, 100667 (2025).","journal-title":"Med"},{"key":"549_CR210","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1186\/s13287-022-03130-5","volume":"13","author":"ZA Li","year":"2022","unstructured":"Li, Z. A. & Tuan, R. S. Towards establishing human body-on-a-chip systems. Stem Cell Res. Ther. 13, 431 (2022).","journal-title":"Stem Cell Res. Ther."},{"key":"549_CR211","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s13075-025-03561-4","volume":"27","author":"E Reihs","year":"2025","unstructured":"Reihs, E. et al. Beyond symptomatic alignment: evaluating the integration of causal mechanisms in matching animal models with human pathotypes in osteoarthritis research. Arthritis Res. Ther. 27, 109 (2025).","journal-title":"Arthritis Res. Ther."},{"key":"549_CR212","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1016\/j.joca.2016.07.017","volume":"24","author":"MA Karsdal","year":"2016","unstructured":"Karsdal, M. A. et al. Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future. Osteoarthr. Cartil. 24, 2013\u20132021 (2016).","journal-title":"Osteoarthr. Cartil."},{"key":"549_CR213","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1007\/s11684-025-1143-5","volume":"19","author":"L Li","year":"2025","unstructured":"Li, L. et al. Understanding pain heterogeneity in osteoarthritis patients: a narrative review. Front. Med. 19, 769\u2013788 (2025).","journal-title":"Front. Med."},{"key":"549_CR214","doi-asserted-by":"crossref","unstructured":"Roman-Blas, J. A., Mendoza-Torres, L. A., Largo, R. & Herrero-Beaumont, G. Setting up distinctive outcome measures for each osteoarthritis phenotype. Ther. Adv. Musculoskelet. Dis. 12, 1759720x20937966 (2020).","DOI":"10.1177\/1759720X20937966"},{"key":"549_CR215","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1080\/03008207.2025.2541291","volume":"66","author":"PMJ Welsing","year":"2025","unstructured":"Welsing, P. M. J. et al. Omics-driven insights into the molecular pathways driving osteoarthritis pathogenesis. Connect Tissue Res. 66, 323\u2013330 (2025).","journal-title":"Connect Tissue Res."},{"key":"549_CR216","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s13075-025-03563-2","volume":"27","author":"Y Liu","year":"2025","unstructured":"Liu, Y., Molchanov, V., Brass, D. & Yang, T. Recent advances in omics and the integration of multi-omics in osteoarthritis research. Arthritis Res. Ther. 27, 100 (2025).","journal-title":"Arthritis Res. Ther."},{"key":"549_CR217","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41413-025-00423-2","volume":"13","author":"J Ou","year":"2025","unstructured":"Ou, J. et al. Advancing osteoarthritis research: the role of AI in clinical, imaging and omics fields. Bone Res 13, 48 (2025).","journal-title":"Bone Res"}],"container-title":["Bone Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41413-026-00549-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41413-026-00549-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41413-026-00549-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:09:11Z","timestamp":1783415351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41413-026-00549-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":217,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["549"],"URL":"https:\/\/doi.org\/10.1038\/s41413-026-00549-x","relation":{},"ISSN":["2095-6231"],"issn-type":[{"value":"2095-6231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"assertion":[{"value":"8 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"72"}}