| Mechanism of signal transduction in tumor necrosis factor-like weak inducer of apoptosis-induced matrix degradation by MMP-3 upregulation in disc tissues. | |
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MedLine Citation:
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PMID: 18923335 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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STUDY DESIGN: Molecular biologic and immuno-histologic analyses using in vitro murine intervertebral disc tissue culture. OBJECTIVE: To investigate the role of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in matrix metalloproteinase 3 (MMP-3) pathway induction, and the effect of TWEAK to induce other cytokines or angiogenesis factors in disc tissues. SUMMARY OF BACKGROUND DATA: We previously demonstrated that TWEAK and its receptor Fn14 were expressed in murine disc tissues. TWEAK induced MMP-3 upregulation and aggrecan downregulation in disc tissues. METHODS: Enzyme-Linked ImmunoSorbent Assay (ELISA), western blot, and immuno-histologic analyses were used to assess the role of TWEAK-induced MMP-3, using murine disc tissue culture. RESULTS: TWEAK induced disc cells to generate MMP-3 as did TNF-alpha and IL-1beta. MMP-3 activity was detectable in murine disc cells. MMP-3 induction was markedly inhibited with a c-Jun N-terminal kinase (JNK) inhibitor. Phosphorylation of JNK was also confirmed. Introduction of TWEAK resulted in the degradation of disc matrix in organ disc culture, whereas proteoglycan degradation was markedly abrogated in the presence of an MMP-3 specific inhibitor or a JNK inhibitor. In addition, TWEAK also induced monocyte chemotactic protein (MCP)-1 via the NF-kappaB pathway, as phosphorylation of NF-kappaB was confirmed by western blotting. CONCLUSION: TWEAK plays an important role in MMP-3 induction in murine disc cells via JNK that results in degradation of disc matrix. TWEAK also induces MCP-1, which belongs to the chemokine family that recruits inflammatory cells via the NF-kappaB pathway. |
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Authors:
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Masanori Wako; Tetsuro Ohba; Takashi Ando; Yoshiyasu Arai; Kensuke Koyama; Yoshiki Hamada; Atsuhito Nakao; Hirotaka Haro |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Spine Volume: 33 ISSN: 1528-1159 ISO Abbreviation: Spine Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-11-03 Completed Date: 2009-02-10 Revised Date: 2009-07-09 |
Medline Journal Info:
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Nlm Unique ID: 7610646 Medline TA: Spine (Phila Pa 1976) Country: United States |
Other Details:
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Languages: eng Pagination: 2489-94 Citation Subset: IM |
Affiliation:
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Department of Orthopaedic Surgery, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Aggrecans
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metabolism Animals Anthracenes / pharmacology Apoptosis / drug effects* Benzamides / pharmacology Enzyme Induction Enzyme Inhibitors / pharmacology Enzyme-Linked Immunosorbent Assay Extracellular Matrix / drug effects*, metabolism Flavonoids / pharmacology Immunoenzyme Techniques Intervertebral Disk / drug effects*, metabolism Matrix Metalloproteinase 3 / metabolism* Mice Mice, Inbred C57BL Recombinant Proteins / pharmacology Signal Transduction* Tissue Culture Techniques Tumor Necrosis Factor-alpha / pharmacology Tumor Necrosis Factors / metabolism*, pharmacology Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Aggrecans; 0/Anthracenes; 0/Benzamides; 0/Enzyme Inhibitors; 0/Flavonoids; 0/N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide; 0/PD 98059; 0/Recombinant Proteins; 0/Tnfsf12 protein, mouse; 0/Tumor Necrosis Factor-alpha; 0/Tumor Necrosis Factors; 0/anthra(1,9-cd)pyrazol-6(2H)-one; EC 3.4.24.17/Matrix Metalloproteinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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