Injury-related cell death and proteoglycan loss in articular cartilage: Numerical model combining necrosis, reactive oxygen species, and inflammatory cytokines

Abstract

Osteoarthritis is one of the most common musculoskeletal diseases. When osteoarthritis develops after a joint injury, it is designated as post-traumatic osteoarthritis. A defining feature of osteoarthritis is degeneration of articular cartilage, which is partly driven by cartilage cells after joint injury, and further accelerated by inflammation. The degeneration triggered by these biomechanical and biochemical mechanisms is currently irreversible. Thus, early prevention/mitigation of disease progression is a key to avoiding PTOA. Prior computational models have been developed to provide insights into the complex mechanisms of cartilage degradation, but they rarely include cell-level cartilage degeneration mechanisms. Here, we present a novel approach to simulate how the early post-traumatic biomechanical and inflammatory effects on cartilage cells eventually influence tissue composition. Our model includes the key regulators of early post-traumatic osteoarthritis: chondral lesions, cell death, reactive oxygen species, and inflammatory cytokines. The model is supported by several experimental explant culture findings. Interestingly, we found that when post-injury inflammation is mitigated, cartilage composition can partially recover. We suggest that mechanobiological models including cell–tissue-level mechanisms can serve as future tools for evaluating high-risk lesions and developing new intervention strategies.

This dataset includes the files needed to run the computational models.

Osteoarthritis is one of the most common musculoskeletal diseases. When osteoarthritis develops after a joint injury, it is designated as post-traumatic osteoarthritis. A defining feature of osteoarthritis is degeneration of articular cartilage, which is partly driven by cartilage cells after joint injury, and further accelerated by inflammation. The degeneration triggered by these biomechanical and biochemical mechanisms is currently irreversible. Thus, early prevention/mitigation of disease progression is a key to avoiding PTOA. Prior computational models have been developed to provide insights into the complex mechanisms of cartilage degradation, but they rarely include cell-level cartilage degeneration mechanisms. Here, we present a novel approach to simulate how the early post-traumatic biomechanical and inflammatory effects on cartilage cells eventually influence tissue composition. Our model includes the key regulators of early post-traumatic osteoarthritis: chondral lesions, cell death, reactive oxygen species, and inflammatory cytokines. The model is supported by several experimental explant culture findings. Interestingly, we found that when post-injury inflammation is mitigated, cartilage composition can partially recover. We suggest that mechanobiological models including cell–tissue-level mechanisms can serve as future tools for evaluating high-risk lesions and developing new intervention strategies.

This dataset includes the files needed to run the computational models.