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Intervertebral disc degeneration (IVDD) is mainly associated with a chronic process of the nucleus pulposus (NP) cells disabled. Also, it is accepted to be the basic result of low back pain. The role of phosphatase and tensin homolog (PTEN) in negatively regulating the Akt/PKB signaling, which is the major cell survival pathway, has been documented in previous studies. The present work aimed to investigate the role of PTEN inhibitor VO-OHpic (VO) in the protection of IVDD and to explore its potential mechanisms.