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

Background 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 catalytic activity for ROS. Its nanoscale particle size and non-stringent catalytic reaction conditions might address challenges faced by traditional antioxidants in remaining stable when used in the degenerative avascular intervertebral disc (IVD). Methods We co-cultured three kinds of IVD cells (cells of annulus fibrosus (AF), cartilage endplate (CEP) and nucleus pulposus (NP) with CeNPs to find the safe concentration range of CeNPs. Additionally, Cell Counting Kit-8 (CCK-8) assay and Calcein/PI staining were performed to detect the protective effect of CeNPs on IVD cells against OS in vitro. Histological and immunohistochemical studies were implemented to analyze the capacity of CeNPs to prevent IDD induced by OS. Then Western blotting was used to explore the corresponding mechanisms. Results The results showed that ≤40 µM was a safe concentration range of CeNPs for the three kinds of IVD cells. CeNPs could alleviate cell proliferation inhibition and reduce cell death caused by OS. Additionally, OS-induced degeneration of each part of the IVD was relieved after being pretreated with CeNPs. These improvements might be achieved through reduced OS-mediated cellular inflammatory response, extracellular matrix (ECM) catabolism and apoptosis. Conclusion This study confirms that CeNPs offer a promising potential strategy for clinical application against OS-induced IDD. Taking CeNPs as an example, the necessity for IDD drug development to take various structures and cells of IVD as well as adjacent tissues around IVD into consideration is clarified.