Microrna-155 Suppresses The Catabolic Effect Induced By Tnf-Alpha And Il-1 Beta By Targeting C/Ebp Beta In Rat Nucleus Pulposus Cells

Aim: miR-155 is a pro-inflammatory or anti-inflammatory factor depending on the cell type in which it is expressed. miR-155 controls apoptosis and matrix degradation in nucleus pulposus (NP) cells in vitro. The aim of this study is to explore the effect of miR-155 in vivo and further investigate the mechanism of miR-155 in vitro. Methods: MRI, hematoxylin-eosin staining, or Collagen-II immunochemistry were performed to observe intervertebral disk degeneration in conditional miR-155 overexpression mice and miR-155 knockout mice. In vitro, a dual luciferase reporter assay, real-time PCR and western blot experiments were performed to demonstrate the effect of miR-155 on the expression of catabolic genes induced by inflammatory cytokines and determine the role of beta-catenin and C/EBP beta in the miR-155-mediated modulation of the expression of catabolic genes. Results: Degeneration was observed in the lumbar disks of 1-year-old miR-155 knockout mice but not in the conditional miR-155 overexpression mice. miR-155 overexpression repressed the catabolic effect induced by TNF-alpha or IL-1 beta in vitro. Furthermore, specifically in NP cells, miR-155 overexpression suppressed the expression of C/EBP beta but not of beta-catenin. Additionally, in the loss-of-function experiments using C/EBP beta siRNA, C/EBP beta knockdown repressed the expression of catabolic genes induced by TNF-alpha and IL-1 beta, which is consistent with the miR-155 results. Conclusion: miR-155 is a sustainable factor for intervertebral disk and suppresses the expression of catabolic genes induced by TNF-alpha and IL-1 beta by targeting C/EBP beta in rat NP cells.