Objective: To investigate the role of TUG1 in intervertebral disc degeneration (IDD) and human nucleus pulposus cells (NPCs) via regulating Wnt/beta-catenin pathway. Methods: The study collected nucleus pulposus (NP) tissue samples from 30 patients with lumbar disc herniation (LDH) (Case group) and 18 patients with lumbar spine trauma (Control group). NPCs induced by TNE-alpha in vitro were divided into Blank, Vector, TUG1, TUG1-siRNA, XAV-939, TUGI + XAV-939 groups. qRT-PCR was used to detect the expression of TUG1 and ECM-related genes, Western blot to determine the expression of Wnt/beta-catenin pathway and apoptosis-related proteins, and ELISA to measure the expression of ECM-related proteins. The apoptosis was detected by TUNEL and Annexin V-FITC/PI double-staining. The proliferation and senescence were tested by CCK-8 and SA-beta-gal staining respectively. Results: TUGI was upregulated in patients with IDD, which was positively related to Wnt and beta-catenin. Besides, TUG1, Wntl and beta-catenin were greatly increased in the NPCs after TNE-alpha induction. Compared with the Blank group, TUG/-siRNA and XAV-939 can appreciably down-regulate the expressions of Wnt1, beta-catenin, Caspase-3, Bax, MMP3 and ADAMTS5, up-regulate the expression of Bcl-2, Aggrecan and COL2A1, inhibit the apoptosis and senescence, and promote cell proliferation; however, the TUGI group had the completely opposite results. Conclusion: Silencing TUGI may not only protect human NPCs from TNF-alpha-induced apoptosis and senescence, but also promote cell proliferation by blocking Wnt/beta-catenin pathway, which provides a theoretical basis for the clinical treatment of IDD. (C) 2017 Elsevier Inc. All rights reserved.