Connective Tissue Research   2015 年 56 卷 6 期

2015.11.02

Tumor necrosis factor-?± (TNF-?±) has been shown to have a catabolic effect on intervertebral disc degeneration (IVDD), including increasing MMP3 expression and subsequent extracellular matrix (ECM) degradation. In contrast, transforming growth factor-??1 (TGF-??1) has an anabolic effect on nucleus pulposus (NP) cells. However, the anti-catabolic effect of TGF-??1 under inflammatory condition is unknown. The aim of this study was to demonstrate whether TGF-??1 can reverse TNF-?±-induced MMP3 increase in NP cells and to further investigate the underlying mechanisms. The transcriptional activity, gene expression, and protein levels of MMP3 were measured by luciferase reporter assay, qRT-PCR and western blot, respectively. TNF-?± increased MMP3 expression in rat NP cells time and dose dependently. TGF-??1 could abolish TNF-?±-mediated up-regulation of collagen I and MMP3 expression, and down-regulate aggrecan and collagen II expression. The ERK1/2 signaling pathway was activated after exposure to TGF-??1. Treatment with ERK1/2 inhibitors (PD98059 and U0126) abolished the antagonistic effect of TGF-??1 on TNF-?± mediated catabolic responses. These findings provide novel evidence supporting the anti-catabolic role of TGF-??1 in IVDD, which is important for the potential clinical application of TGF-??1 in disc degenerative disorders.