TGF-β1 antagonizes TNF-α induced up-regulation of matrix metalloproteinase 3 in nucleus pulposus cells: role of the ERK1/2 pathway

被引:57
作者
Yang, Hao [1 ,2 ]
Gao, Fei [3 ]
Li, Xiang [4 ]
Wang, Jianru [2 ]
Liu, Hui [2 ]
Zheng, Zhaomin [2 ]
机构
[1] Peking Univ, Beijing Jishuitan Hosp, Dept Spine Surg, Beijing 100871, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Spine Surg, Guangzhou 510080, Guangdong, Peoples R China
[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Orthopaed Surg, Wuhan 430074, Peoples R China
[4] First Peoples Hosp Taizhou, Dept Orthopaed, Taizhou, Peoples R China
基金
中国国家自然科学基金;
关键词
ERK1/2 signaling pathway; intervertebral disc degeneration; matrix metalloproteinases; transforming growth factor-1; tumor necrosis factor-alpha; INTERVERTEBRAL DISC DEGENERATION; NECROSIS-FACTOR-ALPHA; LOW-BACK-PAIN; KAPPA-B; EXPRESSION; TISSUE; DEGRADATION; INHIBITORS; IL-1-BETA; ENZYMES;
D O I
10.3109/03008207.2015.1054030
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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.
引用
收藏
页码:461 / 468
页数:8
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