title: TGF-β1 antagonizes TNF-α induced up-regulation of matrix metalloproteinase 3 in nucleus pulposus cells: role of the ERK1/2 pathway.
abstract: Tumor necrosis factor-α (TNF-α) 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-β1 (TGF-β1) has an anabolic effect on nucleus pulposus (NP) cells. However, the anti-catabolic effect of TGF-β1 under inflammatory condition is unknown. The aim of this study was to demonstrate whether TGF-β1 can reverse TNF-α-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-α increased MMP3 expression in rat NP cells time and dose dependently. TGF-β1 could abolish TNF-α-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-β1. Treatment with ERK1/2 inhibitors (PD98059 and U0126) abolished the antagonistic effect of TGF-β1 on TNF-α mediated catabolic responses. These findings provide novel evidence supporting the anti-catabolic role of TGF-β1 in IVDD, which is important for the potential clinical application of TGF-β1 in disc degenerative disorders.
authors.affiliation: a Department of Spine Surgery , Beijing Jishuitan Hospital, Peking University , Xinjiekou Dongjie , Beijing , China .|b Department of Spine Surgery , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China .
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: c Department of Orthopaedic Surgery , Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China , and.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: d Department of Orthopaedics , The First People's Hospital of Taizhou , Taizhou , China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: b Department of Spine Surgery , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China .
authors.forename: Jianru
authors.initials: J
authors.lastname: Wang
authors.affiliation: b Department of Spine Surgery , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China .
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: b Department of Spine Surgery , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China .
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000473:pathology; D008159:Lumbar Vertebrae / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D048052:Mitogen-Activated Protein Kinase 3; D019278:Matrix Metalloproteinase 3
keywords: ERK1/2 signaling pathway; intervertebral disc degeneration; matrix metalloproteinases; transforming growth factor-β1; tumor necrosis factor-α