miR-640 aggravates intervertebral disc degeneration via NF-kappa B and WNT signalling pathway

• Authors: Wengang Dong Dong, Air Force Medical University, China; Jun Liu, Disease Control and Prevention Center of PLA’s Southern Theatre Command China; Yang Lv, General Hospital of Lanzhou Military Command, China; Fei Wang, General Hospital of Lanzhou Military Command, China; Tao Liu, Air Force Medical University, China; Siguo Sun, Air Force Medical University, China; Bo Liao, Air Force Medical University, China; Zhen Shu, Emory University; Jixian Qian, Air Force Medical University, China
• Journal Title: CELL PROLIFERATION
• Volume: Volume 52, Number 5
• Publisher: WILEY | 2019-07-25, Pages e12664-e12664
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1111/cpr.12664
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Pharmacy; Health Sciences, Oncology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cell Biology; inflammation; intervertebral disc degeneration; microRNA; nucleus pulposus; WNT signalling pathway; NUCLEUS PULPOSUS CELLS; NECROSIS-FACTOR-ALPHA; LOW-BACK-PAIN; EXPRESSION; INHIBITION; INDUCTION; APOPTOSIS; BURDEN; COSTS

Abstract

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 β-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-κB signalling pathway. In addition, miR-640 targeted to LRP1 and enhances NF-κB signal activity, which built a positive feedback loop. miR-640 inhibited the expression of β-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.