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TNF‑α increases inflammatory factor expression in synovial fibroblasts through the toll‑like receptor‑3‑mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis

  • Authors:
    • Fang‑Yuan Yu
    • Cong‑Qin Xie
    • Chang‑Liang Jiang
    • Ji‑Tong Sun
    • Xun‑Wu Huang

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  • Published online on: April 19, 2018     https://doi.org/10.3892/mmr.2018.8897
  • Pages: 8475-8483
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
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Abstract

Osteoarthritis is a type of joint disease that may lead to other joint diseases. Previous research has demonstrated that tumor necrosis factor (TNF)‑α is associated with osteoarthritis activity and pathology. The possible mechanisms of the TNF‑α‑mediated signaling pathway have not been clearly elaborated in synovial fibroblasts. The present study aimed to investigate the potential mechanisms of TNF‑α in a mouse model of iodoacetate‑induced osteoarthritis. Reverse transcription‑quantitative polymerase chain reaction, ELISA, western blotting and immunohistochemistry were performed to evaluate the role of TNF‑α in the progression of osteoarthritis. The results revealed that the serum levels of TNF‑α, interleukin (IL)‑1β, IL‑4 and IL‑6 were significantly upregulated in a mouse model of iodoacetate‑induced osteoarthritis compared with healthy mice (P<0.01). TNF‑α, IL‑1β, IL‑4 and IL‑6 mRNA and protein levels were also significantly upregulated in synovial fibroblasts in the experimental mice (P<0.01). It was demonstrated that TNF‑α increased pro‑inflammation factors matrix metalloproteinase (MMP)‑3, MMP‑9, nuclear factor (NF)‑κB and receptor activator of NF‑κB ligand (RANKL) in synovial fibroblasts. It was also observed that the toll‑like receptor (TLR)‑3 was significantly upregulated and extracellular signal‑regulated kinase (ERK) and protein kinase B (AKT) were significantly downregulated in synovial fibroblasts in osteoarthritis mice (P<0.01). An in vitro assay demonstrated that TNF‑α inhibitor decreased mRNA and protein levels of IL‑1β, IL‑4 and IL‑6 in synovial fibroblasts. The knockdown of TLR‑3 abolished the TNF‑α upregulated mRNA and protein levels of IL‑1β, IL‑4 and IL‑6 in synovial fibroblasts. In addition, the knockdown of TLR‑3 also reversed TNF‑α‑upregulated ERK and AKT expression in synovial fibroblasts. In vivo assays demonstrated that TNF‑α inhibitor significantly decreased the deposition of IL‑1β, IL‑4 and IL‑6 as well as bone destruction and significantly increased the body weight and osteoarthritis score for osteoarthritic mice (P<0.01). TNF‑α inhibitor decreased TLR‑3 and significantly increased the expression and phosphorylation of ERK and AKT in articular cartilage (P<0.01). In conclusion the results of the present study indicate that TNF‑α serves an essential role in synovial fibroblasts in osteoarthritis, suggesting that inhibition of TNF‑α may decrease inflammation via the TLR‑3‑mediated ERK/AKT signaling pathway in a mouse model of monosodium iodoacetate‑induced osteoarthritis.
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June-2018
Volume 17 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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  • Journal Metrics
  • Impact Factor: 3.4
  • Ranked Medicine Research and Experimental
    (total number of cites)
  • CiteScore: 7.6
  • CiteScore Rank: Q1: #82/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.647
  • SCImago Journal Rank (SJR): 0.781
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Spandidos Publications style
Yu FY, Xie CQ, Jiang CL, Sun JT and Huang XW: TNF‑α increases inflammatory factor expression in synovial fibroblasts through the toll‑like receptor‑3‑mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis. Mol Med Rep 17: 8475-8483, 2018.
APA
Yu, F., Xie, C., Jiang, C., Sun, J., & Huang, X. (2018). TNF‑α increases inflammatory factor expression in synovial fibroblasts through the toll‑like receptor‑3‑mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis. Molecular Medicine Reports, 17, 8475-8483. https://doi.org/10.3892/mmr.2018.8897
MLA
Yu, F., Xie, C., Jiang, C., Sun, J., Huang, X."TNF‑α increases inflammatory factor expression in synovial fibroblasts through the toll‑like receptor‑3‑mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis". Molecular Medicine Reports 17.6 (2018): 8475-8483.
Chicago
Yu, F., Xie, C., Jiang, C., Sun, J., Huang, X."TNF‑α increases inflammatory factor expression in synovial fibroblasts through the toll‑like receptor‑3‑mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis". Molecular Medicine Reports 17, no. 6 (2018): 8475-8483. https://doi.org/10.3892/mmr.2018.8897