title: TNF-α and TGF-β1 regulate Syndecan-4 expression in nucleus pulposus cells: role of the mitogen-activated protein kinase and NF-κB pathways.
abstract: Syndecan-4 is emerging as an important player in cell interaction with the extracellular environment and has been shown to be involved in the progression of intervertebral disc degeneration. However, the mechanism of syndecan-4 regulation by TNF-α and the role of TGF-β1 in regulating syndecan-4 expression remain poorly understood in nucleus pulposus (NP) cells. The aim of this study was to investigate these mechanisms. We exposed NP cells to TNF-α and the gene, protein expression, and promoter activity levels of syndecan-4 were measured by qPCR, western blotting, and the luciferase reporter assay, respectively. The activation of the MAPK and NF-κB pathways was detected using western blot analysis. Syndecan-4 expression in rat NP cells was increased by TNF-α, but this was neither time nor dose dependent in response to TNF-α. ERK1/2, JNK, and NF-κB pathways were activated following TNF-α treatment. Treatment with ERK1/2 and NF-κB inhibitors decreased the up-regulation of syndecan-4 by TNF-α. However, JNK inhibition showed no effect on syndecan-4 expression induced by TNF-α. TNF-α mediated up-regulation of syndecan-4 was antagonized by TGF-β1. This study provided evidence for the differential regulation by MAPK and NF-κB pathways in the over-expression of syndecan-4 promoted by TNF-α in NP cells. Our results demonstrate that TGF-β1 exerts anabolic effects on intervertebral discs by inhibiting the expression of syndecan-4.
authors.affiliation: Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou; Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Peking University, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Hehai
authors.initials: H
authors.lastname: Pan
authors.forename: Zemin
authors.initials: Z
authors.lastname: Li
authors.forename: Jianru
authors.initials: J
authors.lastname: Wang
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Zheng
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D053671:Syndecan-4 / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C508307:Sdc4 protein, rat; D053671:Syndecan-4; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4
keywords: Intervertebral disc degeneration; NF-κB pathways; mitogen-activated protein kinase pathways; transforming growth factor-β1; tumor necrosis factor-α, syndecan-4