Nucleus pulposus cells (NPCs) isolated from clinical degenerative intervertebral disc (IVD) tissues were introduced with oe‐p300, oe‐FOXO3, Wnt/β‐catenin agonist 1, C646 (p300/CBP inhibitor), or si‐p300 to explore the functional role of p300 in IDD and to characterize the relationship between p300 and the FOXO3/Sirt1/Wnt/β‐catenin pathway. Here, SIRT1 is linked to intervertebral disk degenerative disorder.