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Role of LncRNA TUG1 in intervertebral disc degeneration and nucleus pulposus cells via regulating Wnt/β-catenin signaling pathway
- Source :
- Biochemical and Biophysical Research Communications. 491:668-674
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Objective To investigate the role of TUG1 in intervertebral disc degeneration (IDD) and human nucleus pulposus cells (NPCs) via regulating Wnt/β-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 TNF-α in vitro were divided into Blank, Vector, TUG1 , TUG1 -siRNA, XAV-939, TUG1 + 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/β-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-β-gal staining respectively. Results TUG1 was upregulated in patients with IDD, which was positively related to Wnt and β-catenin. Besides, TUG1 , Wnt1 and β-catenin were greatly increased in the NPCs after TNF-α induction. Compared with the Blank group, TUG1 -siRNA and XAV-939 can appreciably down-regulate the expressions of Wnt1, β-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 TUG1 group had the completely opposite results. Conclusion Silencing TUG1 may not only protect human NPCs from TNF-α-induced apoptosis and senescence, but also promote cell proliferation by blocking Wnt/β-catenin pathway, which provides a theoretical basis for the clinical treatment of IDD.
- Subjects :
- Adult
Male
0301 basic medicine
Senescence
Nucleus Pulposus
Biophysics
Apoptosis
Intervertebral Disc Degeneration
Biology
Biochemistry
Young Adult
03 medical and health sciences
0302 clinical medicine
Western blot
Downregulation and upregulation
Annexin
medicine
Humans
Gene silencing
Wnt Signaling Pathway
Molecular Biology
Cells, Cultured
Cell Proliferation
medicine.diagnostic_test
Cell growth
Wnt signaling pathway
Cell Biology
Anatomy
Middle Aged
Cell biology
030104 developmental biology
Gene Expression Regulation
030220 oncology & carcinogenesis
Female
RNA, Long Noncoding
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 491
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....813875d215457a6d8810dac47cffd17b