Here we focused on typical proteins such as COL2A1, ACAN and SOX9, whose loss is associated with intervertebral disc degeneration, and promising candidates such as FOXO3 and TRPS1 as potential positive modulators of IVD integrity, in order to demonstrate the successful phenotypic change following an effective antagomiR-221 treatment. This evidence concerns the gene COL2A1 and Intervertebral disk degeneration.