A computational framework to model cartilage degeneration induced by mechanoinflammation and cytokine-driven inflammation in post-traumatic osteoarthritis.

Authors

Moustafa Hamada, Atte S A Eskelinen, Joonas P Kosonen, Sanna Hakonen, Cristina Florea, Alan J Grodzinsky, Rami K Korhonen, Petri Tanska

Published in

PLoS computational biology. Volume 22. Issue 11. Pages e1014935. Nov 05, 2026. Epub Nov 05, 2026.

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.

PMID:
42986911
Bibliographic data and abstract were imported from PubMed on 06 Nov 2026.

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