TGF-beta 1 antagonizes TNF-alpha induced up-regulation of matrix metalloproteinase 3 in nucleus pulposus cells: role of the ERK1/2 pathway

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.National Natural Science Foundation of China [81371984]; Natural Science Foundation of Guangdong Province [2014A030313091]SCI(E)PubMedARTICLEhippocratez@163.com; zhengzm1@163.com6461-4685