Programmed NP Cell Death Induced by Mitochondrial ROS in a One-Strike Loading Disc Degeneration Organ Culture Model

This study investigates the impact of mechanical stress on intervertebral discs (IVDs), focusing on cell death and matrix breakdown. The research uses a model that simulates disc degeneration through a single instance of loading. The study also looks at the role of mitochondrial reactive oxygen species (ROS) in this process, exploring how these molecules contribute to cell death and tissue damage in the discs. The experiment involves applying a specific amount of mechanical stress to IVDs and observing the cellular responses over time. Researchers introduced inhibitors to reduce ROS. They examined changes in cell viability, mitochondrial function, and the expression of genes related to cell death and matrix degradation. The findings suggest that mechanical stress leads to increased mitochondrial ROS production, which in turn triggers programmed cell death and matrix degeneration in IVDs. These processes contribute to the early stages of disc degeneration. Reducing mitochondrial ROS levels could potentially prevent or slow down the progression of disc degeneration.

• 1
  Mechanical stress induces mitochondrial dysfunction and ROS accumulation in nucleus pulposus (NP) cells. The proportion of ROS-positive cells increased significantly in the first 12 hours after mechanical stress.
• 2
  Mitochondrial ROS plays a critical role in programmed NP cell death, specifically apoptosis and necroptosis. Pretreatment with MitoQ increased NP cell viability and alleviated the marker changes by 12 hours after mechanical stress.
• 3
  Elevated mitochondrial ROS levels contribute to extracellular matrix (ECM) degeneration, catabolic marker upregulation, anabolic marker downregulation and glycosaminoglycan loss. Pretreatment with MitoQ alleviated some of these degenerative changes by 12 hours after mechanical stress.