Integrated Transcriptomic and Metabolomic Profiling of Cobalt Nanoparticle-Induced Cytotoxicity in THP-1 Macrophages: Implications for Prosthetic Implants

Cobalt, a high-grade metallic substance, is utilized across a wide variety of applications, ranging from joint prostheses to dental fillings. This has increased the level of human exposure to cobalt nanoparticles (CoNPs), potentially causing adverse local tissue reactions and implantation failure. The mechanisms are not fully understood. In this study, a macrophage model of cell exposure to CoNPs was employed to investigate the potential effects of CoNPs on cellular metabolic pathways and gene regulatory networks based on previous explorations on the complications of artificial joint implants. Results showed that CoNPs significantly affected cell membrane components and the expression of genes encoding extracellular matrix proteins. In addition, CoNPs downregulated amino acid metabolism and inhibited pentose metabolism. Based on the observed metabolome and transcriptome alterations, we concluded that the regulatory networks involving pentose and drug metabolism pathways may mediate CoNP-induced toxicity in macrophages. Therefore, beyond inflammatory responses, the combinatorial effects of numerous metabolic regulatory networks may also contribute to CoNP-induced cell damage, particularly in macrophages. These findings provide a deeper insight into the health concerns related to metal nanoparticles of implant materials and emphasize the necessity for safer applications of metal-containing implantable products.