{ "abstract": "Knee joint injury is a major risk factor for post-traumatic osteoarthritis (PTOA), often associated with early cartilage degeneration. Mechanical overloading and cytokine-driven inflammation are key drivers of this process, yet the underlying mechanisms and their distinct temporal and spatial contributions to cartilage degradation remain unclear. Here, we present a mechanobiological finite element framework that simulates cartilage degradation through cell-mediated proteolytic activity triggered by injurious loading-driven mechanoinflammation and cytokine-driven inflammation. The model reproduces experimentally observed depth-dependent loss of collagen and aggrecan, with mechanoinflammation inducing a transient response and cytokine-driven inflammation sustaining prolonged matrix degradation. Sensitivity analysis further shows that mechanoinflammation-driven degradation is governed mainly by protease production per cell, whereas cytokine-driven degradation is more sensitive to the rate of cellular stimulation. Together, this framework provides a mechanistic basis to study proteolytic cartilage degeneration and supports future in silico evaluation of therapeutic strategies aimed at mitigating cartilage degradation in PTOA. Author summary: In this work, we investigate how articular cartilage deteriorates following joint injury, a process that may lead to the development of post-traumatic osteoarthritis. Although joint function may recover after the trauma, cartilage damage can continue to progress without noticeable symptoms. This degeneration is characterized by gradual collagen and aggrecan loss, which are critical for maintaining the structure and mechanical function of the tissue. To better understand this process, we developed a computational model that simulates the loss of collagen and aggrecan after injury and captures how tissue damage varies through cartilage depth. The model focuses on two major pathways that contribute to degeneration. The first, mechanoinflammation, is triggered by mechanical overloading during injury, which stimulates cartilage cells to produce matrix-degrading proteases. The second, inflammation, is driven by inflammatory cytokines that infiltrate to the tissue and stimulate cells to produce matrix-degrading proteases. Using this framework, we were able to distinguish how these pathways contribute to protease production over time and identify when each mechanism becomes the dominant driver of tissue degradation. Overall, this work provides a computational tool that improves our understanding of cartilage degeneration following joint injury and may help evaluate potential anti-inflammatory therapies aimed at slowing or preventing disease progression.", "abstract_shown": true, "affiliations": [ "Department of Technical Physics, University of Eastern Finland, Kuopio, Finland", "Departments of Biological Engineering, Electrical Engineering and Computer Science, and Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America", "Australian Centre for Precision Health and Technology (PRECISE), Griffith University, Gold Coast, Queensland, Australia", "Clinical Research Center, Kuopio University Hospital, Wellbeing Services County of North Savo, Kuopio, Finland", "Department of Oncology, Kuopio University Hospital, Wellbeing Services County of North Savo, Kuopio, Finland" ], "article_type": "Research Article", "arxiv": null, "author_total": 8, "authors": [ { "affs": [ 0 ], "name": "Moustafa Hamada" }, { "affs": [ 1 ], "name": "Atte S. A. Eskelinen" }, { "affs": [ 2 ], "name": "Joonas P. Kosonen" }, { "affs": [ 3 ], "name": "Sanna Hakonen" }, { "affs": [ 4 ], "name": "Cristina Florea" }, { "name": "Alan J. Grodzinsky" }, { "name": "Rami K. Korhonen" }, { "name": "Petri Tanska" } ], "bibtex": "https://research.draconitic.com/paper/23rggg8wxd4rg.bib", "cited_by": 0, "doi": "10.1371/journal.pcbi.1014935", "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014935", "id": "23rggg8wxd4rg", "issns": [ "1553-7358" ], "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014935", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "plos", "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Cartilage" ], [ "plos", "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Cartilage/Chondrocytes" ], [ "plos", "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Chondrocytes" ], [ "plos", "/Biology and life sciences/Biochemistry/Enzymology/Enzymes/Proteases" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Collagens" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Enzymes/Proteases" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular structures and organelles/Extracellular matrix" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Connective tissue cells/Chondrocytes" ], [ "plos", "/Biology and life sciences/Developmental biology/Molecular development/Cytokines" ], [ "plos", "/Biology and life sciences/Immunology/Immune response/Inflammation" ], [ "plos", "/Biology and life sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Cytokines" ], [ "plos", "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Cartilage" ], [ "plos", "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Cartilage/Chondrocytes" ], [ "plos", "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Chondrocytes" ], [ "plos", "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Inflammation" ], [ "plos", "/Medicine and health sciences/Critical care and emergency medicine/Trauma medicine/Traumatic injury" ], [ "plos", "/Medicine and health sciences/Immunology/Immune response/Inflammation" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system/Innate immune system/Cytokines" ] ], "openalex": null, "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014935&type=printable", "pmcid": null, "pmid": null, "published": "2026-11-05", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/23rggg8wxd4rg.ris", "sources": [ { "first_seen": "2026-11-06T12:20:42Z", "native_id": "10.1371/journal.pcbi.1014935", "source": "plos", "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014935" } ], "subjects": [ { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" }, { "field": "medicine", "origin": "plos:anatomy", "subfield": "physiology" } ], "title": "A computational framework to model cartilage degeneration induced by mechanoinflammation and cytokine-driven inflammation in post-traumatic osteoarthritis", "title_text": "A computational framework to model cartilage degeneration induced by mechanoinflammation and cytokine-driven inflammation in post-traumatic osteoarthritis", "type": "peer-reviewed", "updated_at": "2026-11-07T12:20:24Z", "url": "https://research.draconitic.com/paper/23rggg8wxd4rg", "venue": "PLOS Computational Biology", "versions": [] }