{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T07:27:57Z","timestamp":1780730877545,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013209","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"crossref","award":["363459"],"award-info":[{"award-number":["363459"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"crossref","award":["354916"],"award-info":[{"award-number":["354916"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF21OC0065373"],"award-info":[{"award-number":["NNF21OC0065373"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State Research Funding for university-level health research, Kuopio University Hospital, Wellbeing Service County of North Savo","award":["5203080"],"award-info":[{"award-number":["5203080"]}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00c3\u00a9liuksen S\u00c3\u00a4\u00c3\u00a4ti\u00c3\u00b6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022768","name":"Maire Lisko Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022768","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004212","name":"P\u00c3\u00a4ivikki ja Sakari Sohlbergin S\u00c3\u00a4\u00c3\u00a4ti\u00c3\u00b6","doi-asserted-by":"publisher","award":["240074"],"award-info":[{"award-number":["240074"]}],"id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Finnish Ministry of Education and Culture\u00e2\u20ac\u2122s Pilot for Doctoral Programmes"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Collagen damage in articular cartilage plays a key role in post-traumatic osteoarthritis, but the underlying mechanobiological pathways leading to collagen fibril degeneration after injury remain incompletely understood. We hypothesized that mechanical injurious loading induces localized cellular damage in cartilage, which in turn triggers the release of collagen-degrading matrix metalloproteinases (MMPs) and depth-wise collagen loss. To investigate this, we developed a computational mechano-signaling model for injured bovine cartilage, in which injury-induced cell damage is caused by excessive localized shear strains, leading to downstream MMP release, and spatially heterogeneous collagen degradation. The model predictions were compared to\n                    <jats:italic>ex vivo<\/jats:italic>\n                    cartilage explant experiments over 12 days post-injury. By day 12, the simulated bulk and depth-wise collagen loss aligned with our experimental findings quantified via Fourier-transform infrared microspectroscopy imaging (~30% average loss in the model vs.\u2009~\u200935% in the experiment). The results suggest that injury-induced cell damage and the downstream MMP activity can partly explain the depth-wise collagen content loss observed in the early days after cartilage injury. Ultimately, combining the current mechanistic approach with joint-level computational models could enhance the prediction of the onset and progression of cartilage degeneration following joint trauma.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1013209","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T18:49:56Z","timestamp":1768934996000},"page":"e1013209","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["MMP release following cartilage injury leads to collagen loss in intact tissue: A computational study"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4465-8631","authenticated-orcid":true,"given":"Moustafa","family":"Hamada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1516-3083","authenticated-orcid":true,"given":"Atte S. A.","family":"Eskelinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joonas P.","family":"Kosonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Florea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J.","family":"Grodzinsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petri","family":"Tanska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami K.","family":"Korhonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"issue":"11","key":"pcbi.1013209.ref001","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":"J Lieberthal","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"pcbi.1013209.ref002","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13075-020-02156-5","article-title":"Post-traumatic osteoarthritis following ACL injury","volume":"22","author":"L-J Wang","year":"2020","journal-title":"Arthritis Res Ther"},{"issue":"2","key":"pcbi.1013209.ref003","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1097\/01.bor.0000151406.64393.00","article-title":"Joint injury causes knee osteoarthritis in young adults","volume":"17","author":"EM Roos","year":"2005","journal-title":"Curr Opin Rheumatol"},{"issue":"1","key":"pcbi.1013209.ref004","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1010337","article-title":"Injury-related cell death and proteoglycan loss in articular cartilage: Numerical model combining necrosis, reactive oxygen species, and inflammatory cytokines","volume":"19","author":"JP Kosonen","year":"2023","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1013209.ref005","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.freeradbiomed.2022.06.223","article-title":"Extracellular biomolecular free radical formation during injury","volume":"188","author":"MR Hines","year":"2022","journal-title":"Free Radic Biol Med"},{"issue":"3","key":"pcbi.1013209.ref006","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1002\/art.20101","article-title":"Mechanisms and kinetics of glycosaminoglycan release following in vitro cartilage injury","volume":"50","author":"MA DiMicco","year":"2004","journal-title":"Arthritis Rheum"},{"issue":"1","key":"pcbi.1013209.ref007","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1177\/1947603511421155","article-title":"Response of Chondrocytes to Local Mechanical Injury in an Ex Vivo Model","volume":"3","author":"JR Lyman","year":"2012","journal-title":"Cartilage"},{"key":"pcbi.1013209.ref008","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fbioe.2016.00080","article-title":"Linking Cellular and Mechanical Processes in Articular Cartilage Lesion Formation: A Mathematical Model","volume":"4","author":"GI Kapitanov","year":"2016","journal-title":"Front Bioeng Biotechnol"},{"issue":"12","key":"pcbi.1013209.ref009","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1016\/j.joca.2019.07.018","article-title":"Chondrocyte viability is lost during high-rate impact loading by transfer of amplified strain, but not stress, to pericellular and cellular regions","volume":"27","author":"PF Argote","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"key":"pcbi.1013209.ref010","doi-asserted-by":"crossref","first-page":"4698","DOI":"10.1038\/srep04698","article-title":"Cell death stages in single apoptotic and necrotic cells monitored by Raman microspectroscopy","volume":"4","author":"E Brauchle","year":"2014","journal-title":"Sci Rep"},{"issue":"4","key":"pcbi.1013209.ref011","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1600-0838.2009.00912.x","article-title":"Signalling cascades in mechanotransduction: cell-matrix interactions and mechanical loading","volume":"19","author":"L Ramage","year":"2009","journal-title":"Scand J Med Sci Sports"},{"issue":"4","key":"pcbi.1013209.ref012","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/jor.1100160415","article-title":"Effects of injurious compression on matrix turnover around individual cells in calf articular cartilage explants","volume":"16","author":"TM Quinn","year":"1998","journal-title":"J Orthop Res"},{"issue":"7","key":"pcbi.1013209.ref013","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1172\/JCI119316","article-title":"Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage","volume":"99","author":"RC Billinghurst","year":"1997","journal-title":"J Clin Invest"},{"key":"pcbi.1013209.ref014","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.matbio.2018.05.008","article-title":"Osteoarthritis as a disease of the cartilage pericellular matrix","author":"F Guilak","year":"2018","journal-title":"Matrix Biol"},{"issue":"4","key":"pcbi.1013209.ref015","first-page":"285","article-title":"Pathogenetic mechanisms of posttraumatic osteoarthritis: opportunities for early intervention","volume":"4","author":"WC Kramer","year":"2011","journal-title":"Int J Clin Exp Med"},{"issue":"11","key":"pcbi.1013209.ref016","doi-asserted-by":"crossref","first-page":"26035","DOI":"10.3390\/ijms161125943","article-title":"Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis","volume":"16","author":"HS Hwang","year":"2015","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pcbi.1013209.ref017","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/art.39460","article-title":"Injurious Loading of Articular Cartilage Compromises Chondrocyte Respiratory Function","volume":"68","author":"MC Coleman","year":"2016","journal-title":"Arthritis Rheumatol"},{"issue":"10","key":"pcbi.1013209.ref018","doi-asserted-by":"crossref","first-page":"5633","DOI":"10.4049\/jimmunol.163.10.5633","article-title":"Active Matrix Metalloproteinases Are Present in Cartilage During Immune Complex-Mediated Arthritis: A Pivotal Role for Stromelysin-1 in Cartilage Destruction","volume":"163","author":"J van Meurs","year":"1999","journal-title":"The Journal of Immunology"},{"issue":"5","key":"pcbi.1013209.ref019","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.matbio.2010.02.004","article-title":"Matrix metalloproteinase-3 in articular cartilage is upregulated by joint immobilization and suppressed by passive joint motion","volume":"29","author":"DJ Leong","year":"2010","journal-title":"Matrix Biol"},{"issue":"1","key":"pcbi.1013209.ref020","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1080\/03008200390151954","article-title":"Expression and Activities of Matrix Metalloproteinases under Oscillatory Shear in IL-1-Stimulated Synovial Cells","volume":"44","author":"HB Sun","year":"2003","journal-title":"Connective Tissue Research"},{"issue":"1","key":"pcbi.1013209.ref021","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.joca.2013.10.010","article-title":"A numerical model to study mechanically induced initiation and progression of damage in articular cartilage","volume":"22","author":"SM Hosseini","year":"2014","journal-title":"Osteoarthritis Cartilage"},{"issue":"10","key":"pcbi.1013209.ref022","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s11926-014-0451-6","article-title":"The mechanobiology of articular cartilage: bearing the burden of osteoarthritis","volume":"16","author":"J Sanchez-Adams","year":"2014","journal-title":"Curr Rheumatol Rep"},{"issue":"4","key":"pcbi.1013209.ref023","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.3390\/ijms22041742","article-title":"Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis","volume":"22","author":"Q Hu","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pcbi.1013209.ref024","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/jor.25975","article-title":"Loss of collagen content is localized near cartilage lesions on the day of injurious loading and intensified on day 12","volume":"43","author":"M Hamada","year":"2025","journal-title":"J Orthop Res"},{"issue":"2","key":"pcbi.1013209.ref025","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1006\/abbi.2000.1988","article-title":"Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis","volume":"381","author":"AM Loening","year":"2000","journal-title":"Arch Biochem Biophys"},{"issue":"4","key":"pcbi.1013209.ref026","doi-asserted-by":"crossref","DOI":"10.1186\/ar2013","article-title":"Expression profiling of metalloproteinases and their inhibitors in synovium and cartilage","volume":"8","author":"RK Davidson","year":"2006","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"pcbi.1013209.ref027","doi-asserted-by":"crossref","first-page":"14409","DOI":"10.1038\/s41598-021-93744-1","article-title":"An in vitro investigation to understand the synergistic role of MMPs-1 and 9 on articular cartilage biomechanical properties","volume":"11","author":"A Mixon","year":"2021","journal-title":"Sci Rep"},{"issue":"4","key":"pcbi.1013209.ref028","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1007\/s10237-021-01445-5","article-title":"Computational model of damage-induced growth in soft biological tissues considering the mechanobiology of healing","volume":"20","author":"M Gierig","year":"2021","journal-title":"Biomech Model Mechanobiol"},{"issue":"46","key":"pcbi.1013209.ref029","doi-asserted-by":"crossref","first-page":"45539","DOI":"10.1074\/jbc.M303737200","article-title":"Aggrecan protects cartilage collagen from proteolytic cleavage","volume":"278","author":"MA Pratta","year":"2003","journal-title":"J Biol Chem"},{"key":"pcbi.1013209.ref030","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.abb.2016.02.008","article-title":"Modeling IL-1 induced degradation of articular cartilage","volume":"594","author":"S Kar","year":"2016","journal-title":"Arch Biochem Biophys"},{"issue":"6","key":"pcbi.1013209.ref031","article-title":"Mechanobiological model for simulation of injured cartilage degradation via pro-inflammatory cytokines and mechanical stimulus","volume":"16","author":"ASA Eskelinen","year":"2020","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1013209.ref032","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jmbbm.2013.12.003","article-title":"Poroviscoelastic finite element model including continuous fiber distribution for the simulation of nanoindentation tests on articular cartilage","volume":"32","author":"M Taffetani","year":"2014","journal-title":"J Mech Behav Biomed Mater"},{"key":"pcbi.1013209.ref033","doi-asserted-by":"crossref","first-page":"21415","DOI":"10.1038\/srep21415","article-title":"A Novel Method to Simulate the Progression of Collagen Degeneration of Cartilage in the Knee: Data from the Osteoarthritis Initiative","volume":"6","author":"ME Mononen","year":"2016","journal-title":"Sci Rep"},{"issue":"3","key":"pcbi.1013209.ref034","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0021-9290(03)00267-7","article-title":"Stresses in the local collagen network of articular cartilage: a poroviscoelastic fibril-reinforced finite element study","volume":"37","author":"W Wilson","year":"2004","journal-title":"J Biomech"},{"key":"pcbi.1013209.ref035","doi-asserted-by":"crossref","DOI":"10.7717\/peerj.3468","article-title":"Modeling the effect of blunt impact on mitochondrial function in cartilage: implications for development of osteoarthritis","volume":"5","author":"GI Kapitanov","year":"2017","journal-title":"PeerJ"},{"key":"pcbi.1013209.ref036","doi-asserted-by":"crossref","first-page":"107419","DOI":"10.1016\/j.cmpb.2023.107419","article-title":"A chemo-mechano-biological modeling framework for cartilage evolving in health, disease, injury, and treatment","volume":"231","author":"MM Rahman","year":"2023","journal-title":"Comput Methods Programs Biomed"},{"key":"pcbi.1013209.ref037","doi-asserted-by":"crossref","first-page":"108902","DOI":"10.1016\/j.cmpb.2025.108902","article-title":"Predicting the heterogeneous chemo-mechano-biological degeneration of cartilage using 3-D biphasic finite elements","volume":"270","author":"MM Rahman","year":"2025","journal-title":"Comput Methods Programs Biomed"},{"key":"pcbi.1013209.ref038","doi-asserted-by":"crossref","first-page":"111181","DOI":"10.1016\/j.jbiomech.2022.111181","article-title":"Cyclic loading regime considered beneficial does not protect injured and interleukin-1-inflamed cartilage from post-traumatic osteoarthritis","volume":"141","author":"ASA Eskelinen","year":"2022","journal-title":"J Biomech"},{"issue":"1","key":"pcbi.1013209.ref039","doi-asserted-by":"crossref","first-page":"15599","DOI":"10.1038\/s41598-018-33759-3","article-title":"A novel mechanobiological model can predict how physiologically relevant dynamic loading causes proteoglycan loss in mechanically injured articular cartilage","volume":"8","author":"GA Orozco","year":"2018","journal-title":"Sci Rep"},{"issue":"1","key":"pcbi.1013209.ref040","doi-asserted-by":"crossref","first-page":"14015","DOI":"10.1117\/1.1854131","article-title":"Fourier transform infrared imaging spectroscopy analysis of collagenase-induced cartilage degradation","volume":"10","author":"PA West","year":"2005","journal-title":"J Biomed Opt"},{"issue":"7","key":"pcbi.1013209.ref041","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.bbamem.2006.05.014","article-title":"Fourier transform infrared imaging spectroscopy investigations in the pathogenesis and repair of cartilage","volume":"1758","author":"X Bi","year":"2006","journal-title":"Biochim Biophys Acta"},{"key":"pcbi.1013209.ref042","article-title":"Time-dependent computational model of post-traumatic osteoarthritis to estimate how mechanoinflammatory mechanisms impact cartilage aggrecan content","author":"ASA Eskelinen","year":"2024","journal-title":"PLoS Comput Biol."},{"issue":"6","key":"pcbi.1013209.ref043","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.jbiomech.2004.07.003","article-title":"A fibril-reinforced poroviscoelastic swelling model for articular cartilage","volume":"38","author":"W Wilson","year":"2005","journal-title":"J Biomech"},{"issue":"12","key":"pcbi.1013209.ref044","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.joca.2005.07.008","article-title":"A novel method for determination of collagen orientation in cartilage by Fourier transform infrared imaging spectroscopy (FT-IRIS)","volume":"13","author":"X Bi","year":"2005","journal-title":"Osteoarthritis Cartilage"},{"issue":"2","key":"pcbi.1013209.ref045","doi-asserted-by":"crossref","first-page":"021003","DOI":"10.1115\/1.2898725","article-title":"Importance of collagen orientation and depth-dependent fixed charge densities of cartilage on mechanical behavior of chondrocytes","volume":"130","author":"RK Korhonen","year":"2008","journal-title":"J Biomech Eng"},{"issue":"4","key":"pcbi.1013209.ref046","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.bpj.2011.07.006","article-title":"Contribution of proteoglycan osmotic swelling pressure to the compressive properties of articular cartilage","volume":"101","author":"E Han","year":"2011","journal-title":"Biophys J"},{"issue":"12","key":"pcbi.1013209.ref047","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/S0021-9290(00)00153-6","article-title":"A fibril reinforced nonhomogeneous poroelastic model for articular cartilage: inhomogeneous response in unconfined compression","volume":"33","author":"LP Li","year":"2000","journal-title":"J Biomech"},{"issue":"8","key":"pcbi.1013209.ref048","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1590\/S1807-59322011000800021","article-title":"The metabolic dynamics of cartilage explants over a long-term culture period","volume":"66","author":"EK Moo","year":"2011","journal-title":"Clinics (Sao Paulo)"},{"issue":"5","key":"pcbi.1013209.ref049","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1002\/art.10892","article-title":"Proteoglycan degradation after injurious compression of bovine and human articular cartilage in vitro: interaction with exogenous cytokines","volume":"48","author":"P Patwari","year":"2003","journal-title":"Arthritis Rheum"},{"issue":"6","key":"pcbi.1013209.ref050","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/S0736-0266(01)00033-X","article-title":"Biosynthetic response and mechanical properties of articular cartilage after injurious compression","volume":"19","author":"B Kurz","year":"2001","journal-title":"J Orthop Res"},{"issue":"4","key":"pcbi.1013209.ref051","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s10439-018-1986-x","article-title":"Collagen Damage Location in Articular Cartilage Differs if Damage is Caused by Excessive Loading Magnitude or Rate","volume":"46","author":"L Henao-Murillo","year":"2018","journal-title":"Ann Biomed Eng"},{"issue":"6","key":"pcbi.1013209.ref052","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/S0736-0266(02)00070-0","article-title":"Cyclic compression of cartilage\/bone explants in vitro leads to physical weakening, mechanical breakdown of collagen and release of matrix fragments","volume":"20","author":"M Thibault","year":"2002","journal-title":"J Orthop Res"},{"issue":"6","key":"pcbi.1013209.ref053","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1002\/jor.1100170612","article-title":"Compositional and metabolic changes in damaged cartilage are peak-stress, stress-rate, and loading-duration dependent","volume":"17","author":"CT Chen","year":"1999","journal-title":"J Orthop Res"},{"issue":"3","key":"pcbi.1013209.ref054","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s10237-013-0518-8","article-title":"Strain-dependent oxidant release in articular cartilage originates from mitochondria","volume":"13","author":"MJ Brouillette","year":"2014","journal-title":"Biomech Model Mechanobiol"},{"key":"pcbi.1013209.ref055","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1016\/j.joca.2016.07.019","article-title":"Antioxidative therapy in an ex vivo human cartilage trauma-model: attenuation of trauma-induced cell loss and ECM-destructive enzymes by N-acetyl cysteine","volume":"24","author":"J Riegger","year":"2016","journal-title":"Osteoarthritis Cartilage"},{"key":"pcbi.1013209.ref056","doi-asserted-by":"crossref","first-page":"105","DOI":"10.22203\/eCM.v029a09","article-title":"Postnatal changes to the mechanical properties of articular cartilage are driven by the evolution of its collagen network","volume":"29","author":"AR Gannon","year":"2015","journal-title":"Eur Cell Mater"},{"issue":"9","key":"pcbi.1013209.ref057","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.joca.2007.03.005","article-title":"Age- and site-associated biomechanical weakening of human articular cartilage of the femoral condyle","volume":"15","author":"MM Temple","year":"2007","journal-title":"Osteoarthritis Cartilage"},{"issue":"6","key":"pcbi.1013209.ref058","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1002\/jor.1100180608","article-title":"Biomechanical regulation of matrix metalloproteinase-9 in cultured chondrocytes","volume":"18","author":"G Jin","year":"2000","journal-title":"J Orthop Res"},{"issue":"10","key":"pcbi.1013209.ref059","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1002\/art.24857","article-title":"Mechanical injury potentiates proteoglycan catabolism induced by interleukin-6 with soluble interleukin-6 receptor and tumor necrosis factor alpha in immature bovine and adult human articular cartilage","volume":"60","author":"Y Sui","year":"2009","journal-title":"Arthritis Rheum"},{"key":"pcbi.1013209.ref060","article-title":"The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis","author":"JM Dayer","year":"2003","journal-title":"Rheumatology (Oxford)"},{"key":"pcbi.1013209.ref061","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-3-030-01491-9_4","article-title":"The Role of Synovium and Synovial Fluid in Joint Hemostasis","author":"ML Redondo","year":"2019","journal-title":"Joint Preservation of the Knee"},{"key":"pcbi.1013209.ref062","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/978-3-031-25588-5_3","article-title":"Multiscale In Silico Modeling of Cartilage Injuries","volume":"1402","author":"RK Korhonen","year":"2023","journal-title":"Adv Exp Med Biol"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1013209","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013209","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T18:40:10Z","timestamp":1769625610000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013209"}},"subtitle":[],"editor":[{"given":"Arne","family":"Elofsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1013209","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]}}}