{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:35:27Z","timestamp":1792931727483,"version":"4.5.0"},"reference-count":83,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["oarsiopenjournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Osteoarthritis and Cartilage Open"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.ocarto.2025.100624","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T19:24:26Z","timestamp":1747164266000},"page":"100624","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"title":["Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy"],"prefix":"10.1016","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2262-3802","authenticated-orcid":false,"given":"Peter M.","family":"van der Kraan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ocarto.2025.100624_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2024.102527","article-title":"Biological constraint, evolutionary spandrels and antagonistic pleiotropy","volume":"101","author":"Gems","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.ocarto.2025.100624_bib2","article-title":"How aging causes osteoarthritis: an evolutionary physiology perspective","author":"Gems","year":"2024","journal-title":"Preprintsorg"},{"issue":"2","key":"10.1016\/j.ocarto.2025.100624_bib3","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.arr.2007.10.001","article-title":"Osteoarthritis in the context of ageing and evolution. Loss of chondrocyte differentiation block during ageing","volume":"7","author":"van der Kraan","year":"2008","journal-title":"Ageing Res. Rev."},{"issue":"3","key":"10.1016\/j.ocarto.2025.100624_bib4","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.joca.2011.12.003","article-title":"Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration?","volume":"20","author":"van der Kraan","year":"2012","journal-title":"Osteoarthr. Cartil."},{"key":"10.1016\/j.ocarto.2025.100624_bib5","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/1471-2474-9-116","article-title":"The discordance between clinical and radiographic knee osteoarthritis: a systematic search and summary of the literature","volume":"9","author":"Bedson","year":"2008","journal-title":"BMC Muscoskelet. Disord."},{"issue":"9","key":"10.1016\/j.ocarto.2025.100624_bib6","doi-asserted-by":"crossref","first-page":"e508","DOI":"10.1016\/S2665-9913(23)00163-7","article-title":"Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021","volume":"5","author":"Collaborators","year":"2023","journal-title":"Lancet Rheumatol"},{"key":"10.1016\/j.ocarto.2025.100624_bib7","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.arr.2016.06.005","article-title":"A synopsis on aging-Theories, mechanisms and future prospects","volume":"29","author":"da Costa","year":"2016","journal-title":"Ageing Res. Rev."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/emph\/eoy033","article-title":"Is antagonistic pleiotropy ubiquitous in aging biology?","volume":"2018","author":"Austad","year":"2018","journal-title":"Evol. Med. Public Health"},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s00239-019-09923-2","article-title":"Antagonistic pleiotropy in human disease","volume":"88","author":"Byars","year":"2020","journal-title":"J. Mol. Evol."},{"key":"10.1016\/j.ocarto.2025.100624_bib10","doi-asserted-by":"crossref","first-page":"125","DOI":"10.2307\/4444260","article-title":"Nothing in biology makes Sense except in the light of evolution","volume":"35","author":"Dobzhansky","year":"1973","journal-title":"Am. Biol. Teach."},{"issue":"5","key":"10.1016\/j.ocarto.2025.100624_bib11","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s10067-005-0141-x","article-title":"Osteoarthritis is for the birds","volume":"25","author":"Rothschild","year":"2006","journal-title":"Clin. Rheumatol."},{"issue":"4","key":"10.1016\/j.ocarto.2025.100624_bib12","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1600-0684.1996.tb00214.x","article-title":"Osteoarthritis of the hand in nonhuman primates: a clinical, radiographic, and skeletal survey of Cayo Santiago rhesus macaques","volume":"25","author":"Lim","year":"1996","journal-title":"J. Med. Primatol."},{"issue":"10","key":"10.1016\/j.ocarto.2025.100624_bib13","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1136\/vr.89.10.267","article-title":"The palaeopathology of animal skeletal remains","volume":"89","author":"Harcourt","year":"1971","journal-title":"Vet. Rec."},{"key":"10.1016\/j.ocarto.2025.100624_bib14","first-page":"88","article-title":"Effect of modifiable lifestyle factors on biological aging","volume":"13","author":"Lu","year":"2024","journal-title":"JAR Life"},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s11556-024-00362-7","article-title":"Optimal lifestyle patterns for delaying ageing and reducing all-cause mortality: insights from the UK Biobank","volume":"21","author":"Liu","year":"2024","journal-title":"Eur. Rev. Aging Phys. Act."},{"issue":"4","key":"10.1016\/j.ocarto.2025.100624_bib16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1177\/15563316231193753","article-title":"Relationship of chronic systemic inflammation to both chronic lifestyle-related diseases and osteoarthritis: the case for lifestyle medicine for osteoarthritis","volume":"19","author":"Prather","year":"2023","journal-title":"HSS J."},{"key":"10.1016\/j.ocarto.2025.100624_bib17","doi-asserted-by":"crossref","DOI":"10.3389\/fpubh.2024.1451737","article-title":"The association between accelerated biological aging and the risk of osteoarthritis: a cross-sectional study","volume":"12","author":"He","year":"2024","journal-title":"Front. Public Health"},{"key":"10.1016\/j.ocarto.2025.100624_bib18","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.2147\/DMSO.S216791","article-title":"How western diet and lifestyle drive the pandemic of obesity and civilization diseases","volume":"12","author":"Kopp","year":"2019","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"10.1016\/j.ocarto.2025.100624_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.exger.2023.112314","article-title":"Metabolic syndrome accelerates epigenetic ageing in older adults: findings from the Irish Longitudinal Study on Ageing (TILDA)","volume":"183","author":"McCarthy","year":"2023","journal-title":"Exp. Gerontol."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib20","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines12010242","article-title":"The influence of metabolic syndrome on potential aging biomarkers in participants with metabolic syndrome compared to healthy controls","volume":"12","author":"Holmannova","year":"2024","journal-title":"Biomedicines"},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib21","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s13075-019-2081-x","article-title":"The burden of metabolic syndrome on osteoarthritic joints","volume":"21","author":"Dickson","year":"2019","journal-title":"Arthritis Res. Ther."},{"issue":"3","key":"10.1016\/j.ocarto.2025.100624_bib22","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1007\/s13679-023-00520-5","article-title":"Obesity, metabolic syndrome, and osteoarthritis-an updated review","volume":"12","author":"Sampath","year":"2023","journal-title":"Curr. Obes. Rep."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib23","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/s13075-022-02916-5","article-title":"Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model","volume":"24","author":"Sanada","year":"2022","journal-title":"Arthritis Res. Ther."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib24","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13075-024-03349-y","article-title":"Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice","volume":"26","author":"Poudel","year":"2024","journal-title":"Arthritis Res. Ther."},{"issue":"22","key":"10.1016\/j.ocarto.2025.100624_bib25","doi-asserted-by":"crossref","first-page":"12029","DOI":"10.1073\/pnas.1906713117","article-title":"Evaluation of musculoskeletal phenotype of the G608G progeria mouse model with lonafarnib, pravastatin, and zoledronic acid as treatment groups","volume":"117","author":"Cubria","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"5","key":"10.1016\/j.ocarto.2025.100624_bib26","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/s41419-023-05856-3","article-title":"Accelerated aging in articular cartilage by ZMPSTE24 deficiency leads to osteoarthritis with impaired metabolic signaling and epigenetic regulation","volume":"14","author":"Suo","year":"2023","journal-title":"Cell Death Dis."},{"issue":"24","key":"10.1016\/j.ocarto.2025.100624_bib27","doi-asserted-by":"crossref","first-page":"12793","DOI":"10.18632\/aging.102603","article-title":"Loss of Klotho contributes to cartilage damage by derepression of canonical Wnt\/beta-catenin signaling in osteoarthritis mice","volume":"11","author":"Gu","year":"2019","journal-title":"Aging (Albany NY)"},{"issue":"6","key":"10.1016\/j.ocarto.2025.100624_bib28","first-page":"417","article-title":"Articular aging and osteoarthrosis in dwarf mice","volume":"38","author":"Silberberg","year":"1972","journal-title":"Pathol. Microbiol. (Basel)"},{"issue":"3","key":"10.1016\/j.ocarto.2025.100624_bib29","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s11357-010-9175-3","article-title":"Analysis of osteoarthritis in a mouse model of the progeroid human DNA repair syndrome trichothiodystrophy","volume":"33","author":"Botter","year":"2011","journal-title":"Age (Dordr)"},{"issue":"10","key":"10.1016\/j.ocarto.2025.100624_bib30","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.joca.2016.05.018","article-title":"Unloading results in rapid loss of TGFbeta signaling in articular cartilage: role of loading-induced TGFbeta signaling in maintenance of articular chondrocyte phenotype?","volume":"24","author":"Madej","year":"2016","journal-title":"Osteoarthr. Cartil."},{"issue":"3","key":"10.1016\/j.ocarto.2025.100624_bib31","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrrheum.2016.219","article-title":"The changing role of TGFbeta in healthy, ageing and osteoarthritic joints","volume":"13","author":"van der Kraan","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"issue":"6","key":"10.1016\/j.ocarto.2025.100624_bib32","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0945-053X(98)90103-2","article-title":"Terminal differentiation of chondrocytes is arrested at distinct stages identified by their expression repertoire of marker genes","volume":"17","author":"Szuts","year":"1998","journal-title":"Matrix Biol."},{"key":"10.1016\/j.ocarto.2025.100624_bib33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1749-6632.1990.tb42363.x","article-title":"Hypertrophic chondrocytes. The terminal stage of differentiation in the chondrogenic cell lineage?","volume":"599","author":"Pacifici","year":"1990","journal-title":"Ann. N. Y. Acad. Sci."},{"issue":"2","key":"10.1016\/j.ocarto.2025.100624_bib34","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1046\/j.1469-7580.2002.00085.x","article-title":"Expression of VEGF121 and VEGF165 in hypertrophic chondrocytes of the human growth plate and epiphyseal cartilage","volume":"201","author":"Petersen","year":"2002","journal-title":"J. Anat."},{"issue":"49","key":"10.1016\/j.ocarto.2025.100624_bib35","doi-asserted-by":"crossref","first-page":"17192","DOI":"10.1073\/pnas.0407788101","article-title":"Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification","volume":"101","author":"Inada","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"5","key":"10.1016\/j.ocarto.2025.100624_bib36","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.orthres.2004.01.011","article-title":"Matrix metalloproteinase-9 expression, tartrate-resistant acid phosphatase activity, and DNA fragmentation in vascular and cellular invasion into cartilage preceding primary endochondral ossification in long bones","volume":"22","author":"Takahara","year":"2004","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.ocarto.2025.100624_bib37","article-title":"The role of hypertrophic chondrocytes in regulation of the cartilage-to-bone transition in fracture healing","volume":"17","author":"Kodama","year":"2022","journal-title":"Bone Rep"},{"issue":"5","key":"10.1016\/j.ocarto.2025.100624_bib38","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/joa.12037","article-title":"A new scenario of the evolutionary derivation of the mammalian diaphragm from shoulder muscles","volume":"222","author":"Hirasawa","year":"2013","journal-title":"J. Anat."},{"issue":"2","key":"10.1016\/j.ocarto.2025.100624_bib39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3003044","article-title":"Evolutionary origin of lubricated joints at the dawn of jawed vertebrates","volume":"23","author":"Crump","year":"2025","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ocarto.2025.100624_bib40","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.16415","article-title":"Ancient origin of lubricated joints in bony vertebrates","volume":"5","author":"Askary","year":"2016","journal-title":"Elife"},{"issue":"12","key":"10.1016\/j.ocarto.2025.100624_bib41","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1002\/art.11367","article-title":"Longitudinal analysis of cartilage atrophy in the knees of patients with spinal cord injury","volume":"48","author":"Vanwanseele","year":"2003","journal-title":"Arthritis Rheum."},{"issue":"8","key":"10.1016\/j.ocarto.2025.100624_bib42","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1002\/art.10462","article-title":"Knee cartilage of spinal cord-injured patients displays progressive thinning in the absence of normal joint loading and movement","volume":"46","author":"Vanwanseele","year":"2002","journal-title":"Arthritis Rheum."},{"issue":"4","key":"10.1016\/j.ocarto.2025.100624_bib43","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1620\/tjem.217.271","article-title":"Increased expression of metalloproteinase-8 and -13 on articular cartilage in a rat immobilized knee model","volume":"217","author":"Ando","year":"2009","journal-title":"Tohoku J. Exp. Med."},{"issue":"2","key":"10.1016\/j.ocarto.2025.100624_bib44","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1620\/tjem.224.77","article-title":"Reversibility of immobilization-induced articular cartilage degeneration after remobilization in rat knee joints","volume":"224","author":"Ando","year":"2011","journal-title":"Tohoku J. Exp. Med."},{"issue":"2","key":"10.1016\/j.ocarto.2025.100624_bib45","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1006\/dbio.1993.1200","article-title":"TGF-beta 1 prevents hypertrophy of epiphyseal chondrocytes: regulation of gene expression for cartilage matrix proteins and metalloproteases","volume":"158","author":"Ballock","year":"1993","journal-title":"Dev. Biol."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib46","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1083\/jcb.153.1.35","article-title":"TGF-beta\/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage","volume":"153","author":"Yang","year":"2001","journal-title":"J. Cell Biol."},{"issue":"5","key":"10.1016\/j.ocarto.2025.100624_bib47","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0036964","article-title":"Dynamic compression of chondrocyte-agarose constructs reveals new candidate mechanosensitive genes","volume":"7","author":"Bougault","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ocarto.2025.100624_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2020.115694","article-title":"Bone replaces unloaded articular cartilage during knee immobilization. A longitudinal study in the rat","volume":"142","author":"Watanabe","year":"2021","journal-title":"Bone"},{"key":"10.1016\/j.ocarto.2025.100624_bib49","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.bone.2017.09.018","article-title":"Bone replaces articular cartilage in the rat knee joint after prolonged immobilization","volume":"106","author":"Campbell","year":"2018","journal-title":"Bone"},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib50","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.joca.2015.07.018","article-title":"Ageing is associated with reduction of mechanically-induced activation of Smad2\/3P signaling in articular cartilage","volume":"24","author":"Madej","year":"2016","journal-title":"Osteoarthr. Cartil."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib51","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41584-021-00695-y","article-title":"Joint distraction for osteoarthritis: clinical evidence and molecular mechanisms","volume":"18","author":"Jansen","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"issue":"3","key":"10.1016\/j.ocarto.2025.100624_bib52","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.joca.2019.12.005","article-title":"The molecular profile of synovial fluid changes upon joint distraction and is associated with clinical response in knee osteoarthritis","volume":"28","author":"Watt","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"10.1016\/j.ocarto.2025.100624_bib53","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2020.579751","article-title":"Gene expression signatures of synovial fluid multipotent stromal cells in advanced knee osteoarthritis and following knee joint distraction","volume":"8","author":"Sanjurjo-Rodriguez","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib54","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s42003-020-01520-0","article-title":"A single day of TGF-beta1 exposure activates chondrogenic and hypertrophic differentiation pathways in bone marrow-derived stromal cells","volume":"4","author":"Futrega","year":"2021","journal-title":"Commun. Biol."},{"issue":"10","key":"10.1016\/j.ocarto.2025.100624_bib55","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20102591","article-title":"Therapeutic effects of rAAV-mediated concomittant gene transfer and overexpression of TGF-beta and IGF-I on the chondrogenesis of human bone-marrow-derived mesenchymal stem cells","volume":"20","author":"Morscheid","year":"2019","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib56","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/s10517-022-05513-3","article-title":"Localization of VEGF, TGF-beta1, BMP-2, and apoptosis factors in hypertrophic nonunion of human tubular bones","volume":"173","author":"Kostiv","year":"2022","journal-title":"Bull. Exp. Biol. Med."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib57","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1053\/joca.2002.0863","article-title":"Activation of beta-catenin-LEF\/TCF signal pathway in chondrocytes stimulates ectopic endochondral ossification","volume":"11","author":"Kitagaki","year":"2003","journal-title":"Osteoarthr. Cartil."},{"issue":"2","key":"10.1016\/j.ocarto.2025.100624_bib58","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1083\/jcb.140.2.409","article-title":"Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes","volume":"140","author":"Enomoto-Iwamoto","year":"1998","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.ocarto.2025.100624_bib59","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.95640","article-title":"Cbfbeta regulates Wnt\/beta-catenin, Hippo\/Yap, and Tgfbeta signaling pathways in articular cartilage homeostasis and protects from ACLT surgery-induced osteoarthritis","volume":"13","author":"Chen","year":"2024","journal-title":"Elife"},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib60","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1359\/jbmr.080901","article-title":"Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice","volume":"24","author":"Zhu","year":"2009","journal-title":"J. Bone Miner. Res."},{"issue":"4","key":"10.1016\/j.ocarto.2025.100624_bib61","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.joca.2013.01.009","article-title":"Hypertrophic differentiation during chondrogenic differentiation of progenitor cells is stimulated by BMP-2 but suppressed by BMP-7","volume":"21","author":"Caron","year":"2013","journal-title":"Osteoarthr. Cartil."},{"issue":"2","key":"10.1016\/j.ocarto.2025.100624_bib62","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1530\/JOE-11-0048","article-title":"The skeleton: a multi-functional complex organ: the growth plate chondrocyte and endochondral ossification","volume":"211","author":"Mackie","year":"2011","journal-title":"J. Endocrinol."},{"issue":"10","key":"10.1016\/j.ocarto.2025.100624_bib63","first-page":"1021","article-title":"The hypertrophic chondrocyte: to be or not to be","volume":"36","author":"Hallett","year":"2021","journal-title":"Histol. Histopathol."},{"issue":"16","key":"10.1016\/j.ocarto.2025.100624_bib64","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1101\/gad.13.16.2072","article-title":"Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation","volume":"13","author":"St-Jacques","year":"1999","journal-title":"Genes Dev."},{"issue":"12","key":"10.1016\/j.ocarto.2025.100624_bib65","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/nm.2055","article-title":"Modulating hedgehog signaling can attenuate the severity of osteoarthritis","volume":"15","author":"Lin","year":"2009","journal-title":"Nat. Med."},{"key":"10.1016\/j.ocarto.2025.100624_bib66","doi-asserted-by":"crossref","DOI":"10.1016\/j.gene.2019.143959","article-title":"Low dose of indomethacin and Hedgehog signaling inhibitor administration synergistically attenuates cartilage damage in osteoarthritis by controlling chondrocytes pyroptosis","volume":"712","author":"Liu","year":"2019","journal-title":"Gene"},{"issue":"4","key":"10.1016\/j.ocarto.2025.100624_bib67","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202101791RR","article-title":"Blocking chondrocyte hypertrophy in conditional Evc knockout mice does not modify cartilage damage in osteoarthritis","volume":"36","author":"Lamuedra","year":"2022","journal-title":"FASEB J."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib68","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/art.22475","article-title":"Prognostic factors of progression of osteoarthritis of the knee: a systematic review of observational studies","volume":"57","author":"Belo","year":"2007","journal-title":"Arthritis Rheum."},{"issue":"24","key":"10.1016\/j.ocarto.2025.100624_bib69","doi-asserted-by":"crossref","first-page":"6003","DOI":"10.1016\/j.cell.2021.11.003","article-title":"Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations","volume":"184","author":"Boer","year":"2021","journal-title":"Cell"},{"issue":"4","key":"10.1016\/j.ocarto.2025.100624_bib70","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1097\/00005131-199509040-00001","article-title":"Degenerative arthritis after tibial plateau fractures","volume":"9","author":"Honkonen","year":"1995","journal-title":"J. Orthop. Trauma"},{"issue":"4","key":"10.1016\/j.ocarto.2025.100624_bib71","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1302\/0301-620X.72B4.2380219","article-title":"Degenerative arthritis after intra-articular fractures of the knee. Long-term results","volume":"72","author":"Volpin","year":"1990","journal-title":"J. Bone Joint Surg. Br."},{"issue":"9","key":"10.1016\/j.ocarto.2025.100624_bib72","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.joca.2023.04.010","article-title":"Persistent underloading of patellofemoral joint following hamstring autograft ACL reconstruction is associated with cartilage health","volume":"31","author":"Liao","year":"2023","journal-title":"Osteoarthr. Cartil."},{"key":"10.1016\/j.ocarto.2025.100624_bib73","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ptsp.2023.03.003","article-title":"Knee joint underloading does not evolve after a two-week reintroduction to running program after anterior cruciate ligament reconstruction","volume":"61","author":"Pairot de Fontenay","year":"2023","journal-title":"Phys. Ther. Sport"},{"issue":"11","key":"10.1016\/j.ocarto.2025.100624_bib74","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.joca.2015.08.015","article-title":"Inflammation in joint injury and post-traumatic osteoarthritis","volume":"23","author":"Lieberthal","year":"2015","journal-title":"Osteoarthr. Cartil."},{"issue":"11","key":"10.1016\/j.ocarto.2025.100624_bib75","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.joca.2012.07.021","article-title":"Cartilage and bone markers and inflammatory cytokines are increased in synovial fluid in the acute phase of knee injury (hemarthrosis)--a cross-sectional analysis","volume":"20","author":"Sward","year":"2012","journal-title":"Osteoarthr. Cartil."},{"issue":"5","key":"10.1016\/j.ocarto.2025.100624_bib76","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s11914-018-0477-1","article-title":"Mechanisms of osteoarthritis (OA) pain","volume":"16","author":"O'Neill","year":"2018","journal-title":"Curr. Osteoporos. Rep."},{"issue":"12","key":"10.1016\/j.ocarto.2025.100624_bib77","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1002\/art.42649","article-title":"Relation of intra-articular mineralization to knee pain in knee osteoarthritis: a longitudinal analysis in the MOST study","volume":"75","author":"Liew","year":"2023","journal-title":"Arthritis Rheumatol."},{"issue":"1","key":"10.1016\/j.ocarto.2025.100624_bib78","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4081\/reumatismo.2014.766","article-title":"The sources of pain in osteoarthritis: a pathophysiological review","volume":"66","author":"Salaffi","year":"2014","journal-title":"Reumatismo"},{"key":"10.1016\/j.ocarto.2025.100624_bib79","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.2147\/IJGM.S310050","article-title":"COL2A1 mutation (c.611G>C) leads to early-onset osteoarthritis in a Chinese family","volume":"14","author":"Li","year":"2021","journal-title":"Int. J. Gen. Med."},{"issue":"5","key":"10.1016\/j.ocarto.2025.100624_bib80","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/ng.3816","article-title":"Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis","volume":"49","author":"Styrkarsdottir","year":"2017","journal-title":"Nat. Genet."},{"issue":"5","key":"10.1016\/j.ocarto.2025.100624_bib81","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0096387","article-title":"Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition","volume":"9","author":"Aubart","year":"2014","journal-title":"PLoS One"},{"issue":"11","key":"10.1016\/j.ocarto.2025.100624_bib82","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1016\/j.pain.2013.06.005","article-title":"Rethinking the fear avoidance model: toward a multidimensional framework of pain-related disability","volume":"154","author":"Wideman","year":"2013","journal-title":"Pain"},{"issue":"9","key":"10.1016\/j.ocarto.2025.100624_bib83","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41584-024-01126-4","article-title":"Clinical phenotypes, molecular endotypes and theratypes in OA therapeutic development","volume":"20","author":"Mobasheri","year":"2024","journal-title":"Nat. Rev. Rheumatol."}],"container-title":["Osteoarthritis and Cartilage Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2665913125000603?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2665913125000603?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:59:32Z","timestamp":1759964372000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2665913125000603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":83,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["S2665913125000603"],"URL":"https:\/\/doi.org\/10.1016\/j.ocarto.2025.100624","relation":{},"ISSN":["2665-9131"],"issn-type":[{"value":"2665-9131","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy","name":"articletitle","label":"Article Title"},{"value":"Osteoarthritis and Cartilage Open","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ocarto.2025.100624","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International (OARSI).","name":"copyright","label":"Copyright"}],"article-number":"100624"}}