Journal
CELL PROLIFERATION
Volume 52, Issue 5, Pages -Publisher
WILEY
DOI: 10.1111/cpr.12664
Keywords
inflammation; intervertebral disc degeneration; microRNA; nucleus pulposus; WNT signalling pathway
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Funding
- Science and Technology Research and Development Projects of Shaanxi Province [2016SF-140]
- National Natural Science Foundation of China [31601096, 81871818]
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Objectives Low back pain becomes a common orthopaedic disease today. It is mainly induced by the degeneration of the intervertebral disc. In this study, we tried to reveal the pathogenesis of the degeneration and the relative therapeutic strategy, which are still elusive. Materials and Methods We collected 15 degenerative intervertebral tissues and five healthy donors. Nucleus pulposus and annulus fibrosus cells were subcultured. miR-640 expression was determined by qPCR. Computer analysis and luciferase reporter assay were used to confirm miR-640 target genes. Immunohistochemical and immunocytochemical staining was used to trace the proinflammatory cytokines and key transductor of signalling pathways. We also used beta-galactosidase staining, flow cytometry, and cell viability assay to monitor the degenerative index. Results miR-640 overexpressed in patients derived degenerative nucleus pulposus tissues and cells. The inflammatory environment promoted miR-640 expression via NF-kappa B signalling pathway. In addition, miR-640 targeted to LRP1 and enhances NF-kappa B signal activity, which built a positive feedback loop. miR-640 inhibited the expression of beta-catenin and EP300, therefore, restrained WNT signal and induced the degeneration in nucleus pulposus cells. miR-640 inhibitor treatment exhibited the effects of anti-inflammation, reverse WNT signalling pathway exhaustion, and remission of degenerative characteristics in vitro. Conclusions miR-640 plays an important role in the degeneration of intervertebral disc and the relative inflammatory microenvironment. It is a promising potential therapeutic target for the low back pain biotherapy.
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