Protein phosphatase 2A regulates nucleus pulposus autophagy and aggravates degeneration via the AKT/mTOR pathway.

Protein phosphatase 2A, a serine-threonine phosphatase, plays a pivotal role in diverse cellular processes in eukaryotic cells. In this research, we observed a significant increase in PP2Ac expression in NPCs with higher degeneration grades. In vitro experiments demonstrated that following the induction of NP cell degeneration, PP2Ac expression was elevated. Moreover, promoting PP2Ac expression further decreased the content of Col-2 while increasing the level of MMP13. Additionally, we found elevated levels of LC3B and Bcl-2, alongside a significant decrease in P62. KEGG pathway enrichment analysis of PP2Ac-knockdown cells revealed significant changes in gene expression within the PI3K-AKT and mTOR signaling pathways. In addition, activation of PP2Ac led to a reduction in intervertebral disc height, further diminished disc hydration, and a significant decrease in NP tissue volume in rats. We propose that PP2Ac induces autophagy in NP cells by activating the AKT/mTOR pathway, thereby facilitating NP degeneration.