Elsevier

Biomedicine & Pharmacotherapy

Volume 108, December 2018, Pages 646-655
Biomedicine & Pharmacotherapy

Transcription factor 7-like 2 controls matrix degradation through nuclear factor κB signaling and is repressed by microRNA-155 in nucleus pulposus cells

https://doi.org/10.1016/j.biopha.2018.09.076Get rights and content
Under a Creative Commons license
open access

Abstract

Aim

TCF7L2, a key transcription factor in the canonical Wnt pathway, plays a vital role in the matrix degradation of chondrocytes. However, it is unknown whether TCF7L2 is important in the matrix metabolism of inner gel-like nucleus pulposus (NP) cells; thus, the aim of this study was to explore the effect and mechanism of TCF7L2 in this process.

Methods

Western blotting and immunofluorescence analyses were used to observe TCF7L2 expression in rat and human NP tissues. Real-time PCR and western blotting were performed to detect the expression of TCF7L2 stimulated by inflammatory cytokines. Dual luciferase reporter assay, real-time PCR, western blotting and knockdown experiments were performed to demonstrate the role of NF-κB signaling in matrix regulation by TCF7L2 and the regulation of TCF7L2 by miR-155 in intervertebral disc degeneration.

Key findings

TCF7L2 is present in rat and human NP tissues and is expressed in the nucleus of NP cells. TCF7L2 is refractory to stimulation of rat and human NP cells with the inflammatory cytokines TNF-α and IL-1β, in contrast to the results in other cell types. Loss-of-function experiments using TCF7L2 siRNA or lentiviral shTCF7L2 showed that TCF7L2 knockdown suppresses matrix degradation through p65/NF-κB signaling in the absence and presence of TNF-α. In addition, TCF7L2 expression is repressed by miR-155 overexpression and promoted by miR-155 inhibition.

Significance

Overall, these results demonstrate that the suppression of TCF7L2, which is modulated by miR-155, inhibits matrix degradation through p65/NF-κB signaling. TCF7L2 suppression may have therapeutic potential in intervertebral disc degeneration.

Keywords

Intervertebral disc degeneration
Nucleus pulposus
Transcription factor 7-like 2
Inflammatory cytokines
Nuclear factor κB signaling
microRNA-155

Cited by (0)

1

These authors contributed equally to this work.