Application of cerium dioxide nanoparticles in the treatment of intervertebral disc degeneration induced by oxidative stress.

Oxidative stress (OS) induced by local reactive oxygen species (ROS) accumulation plays a vital role in initiating and accelerating intervertebral disc degeneration (IDD). Cerium oxide nanoparticles (CeNPs) have specific and efficient superoxide dismutase (SOD)-mimicking activity for ROS degradation. Their nanoscale particle size and nonstringent catalytic reaction conditions can potentially address challenges faced by traditional antioxidants in terms of remaining stable when used in degenerative avascular intervertebral disc (IVD). We cocultured three kinds of IVD cells (cells of annulus fibrosus (AF), cartilage endplate (CEP) and nucleus pulposus (NP)) with CeNPs to determine the safe range of CeNPs concentrations. Additionally, Cell Counting Kit-8 (CCK-8) assay, ROS level assay and calcein/PI staining were performed to detect the protective effect of CeNPs on IVD cells against OS in vitro. Transmission electron microscopy (TEM), inductively coupled plasma mass spectrometry (ICP-MS) and blood analysis were used to describe its distribution pattern and the possible effects CeNPs may have on the body. Histological and immunohistochemical studies were implemented to analyse the capacity of CeNPs to prevent IDD induced by OS. Then western blotting was used to explore the corresponding mechanisms. The results showed that ≤ 40 µM CeNPs was safe for the three kinds of IVD cells. CeNPs alleviated the inhibition of cell proliferation and reduced the degree of cell death caused by OS to different degrees. Additionally, the OS-induced degeneration of each part of the IVD was partially relieved after pretreatment with CeNPs. These improvements might be achieved through reducing OS-mediated cellular inflammatory response, extracellular matrix (ECM) catabolism and apoptosis. This study proposes that the local application of CeNPs to the IVD could mitigate OS-induced IDD. Our findings indicate that experimental designs incorporating multiple IVD structures, IVD cells, and surrounding tissues are essential for evaluating drug effect and safety in IDD therapeutic development.