GATA4 promotes the senescence of nucleus pulposus cells via NF-κB pathway

Abstract

PurposeCell senescence plays a vital role in intervertebral disc degeneration. The regulatory mechanism of the cellular senescence of nucleus pulposus cells has not been fully elucidated. A recent study identified GATA4 as an emerging regulator of IMR90 cellular senescence. However, whether GATA4 controls senescence in nucleus pulposus cells still needs to be explored. MethodsNucleus pulposus cells were exposed to acidified medium mimic the acid environment of intervertebral disc degeneration. ResultsWe found that GATA4 protein expression was significantly upregulated in older rats and nucleus pulposus cells undergoing stress-induced aging. Moreover, the data indicated that inhibition of GATA4 significantly inhibited the senescence of nucleus pulposus cells cultured under acidic conditions and that over expression of GATA4 promoted a senescence phenotype. The NF-κB pathway has been confirmed in this study to play a role in the regulation of nucleus pulposus cell senescence by GATA4. By using the NF-κB pathway inhibitor, PDTC (100 μmol/L), significantly decreased the IL-6, matrix metallopeptidase (MMP)-2, MMP-3, MMP-9, MMP-13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4, ADAMTS-5 expression level, and increased Aggrecan and typeⅡcollagen expression level in GATA4 transfected nucleus pulposus cells compared with the group in the absence of PDTC. ConclusionThis outcome suggested that GATA4 might play a significant role in nucleus pulposus cell senescence through the NF-κB signaling pathway, and GATA4 is a promising target for intervertebral disc degeneration treatment in the future.