MMP release following cartilage injury leads to collagen loss in intact tissue: A computational study.

Abstract

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 ex vivo 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. ~ 35% 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.