Nucleus pulposus cell-associated PLAU promotes intervertebral disc degeneration through HIPPO pathway.

Intervertebral disc degeneration (IDD) is the most common and critical pathological basis for various spinal disorders. In this study, we investigated how plasminogen activator urokinase (PLAU) promotes IDD progression through the HIPPO pathway. Bioinformatics analysis showed that PLAU is a hub gene in IDD. Both in vitro and in vivo experiments confirmed that PLAU can promote the apoptosis of nucleus pulposus chondrocytes. PLAU activates the HIPPO signaling pathway by increasing the phosphorylation levels of mammalian ste20-like kinases 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), and yes associated protein (YAP), promoting chondrocyte apoptosis, which is one of the reasons for the accelerated progression of IDD. These findings provide new insights into the role of PLAU in IDD and highlight its potential as a therapeutic target for IDD.