Transcription factor EB mediates oxidative stress-induced intervertebral disc degeneration via the NF-κB signaling pathway.

Abstract

BackgroundIt is well known that the intervertebral disc is aggravated by a significant increase in the number of senescent cells, and oxidative stress (OS) is related to the deterioration of this tissue. Transcription factor EB (TFEB) can protect cells from OS. Accordingly, we investigated whether TFEB can prevent OS in human nucleus pulposus (NP) cells.MethodsFirst, TFEB expression was investigated in human NP tissue samples with different degrees of degeneration. NP cells were treated with different concentrations of hydrogen peroxide (H2O2). The expression of collagen 2, aggrecan, and P65 was detected by quantitative real-time polymerase chain reaction (PCR) and Western blotting. We overexpressed and knocked out the TFEB gene to detect the expression of collagen 2, aggrecan, and P65.ResultsWe found that the expression of TFEB decreased stepwise as the degree of intervertebral disc degeneration (IDD) increased. When the NP cells were treated with H2O2, the expression of TFEB, collagen 2, and aggrecan decreased gradually as H2O2 concentration increased. In addition, the expression of collagen2 and aggrecan increased following TFEB overexpression. However, nuclear factor-kappa B (NF-κB) decreased in NP cells after TFEB overexpression. We also found that the previously low cell viability increased and the high level of apoptosis decreased.ConclusionsThis study suggests that OS is associated with the development of IDD. TFEB mediates OS-induced IDD via the NF-κB signaling pathway. The TFEB gene can potentially be used as a diagnostic biomarker and therapeutic target.