TNF‑α increases the expression of inflammatory factors in synovial fibroblasts by inhibiting the PI3K/AKT pathway in a rat model of monosodium iodoacetate‑induced osteoarthritis

Li,Hongxi; Xie,Shujuan; Qi,Yunlong; Li,Huazhe; Zhang,Rui; Lian,Yongyun

doi:10.3892/etm.2018.6770

TNF‑α increases the expression of inflammatory factors in synovial fibroblasts by inhibiting the PI3K/AKT pathway in a rat model of monosodium iodoacetate‑induced osteoarthritis

Authors:
- Hongxi Li
- Shujuan Xie
- Yunlong Qi
- Huazhe Li
- Rui Zhang
- Yongyun Lian
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Affiliations: Department of Orthopedics, The Fourth Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Community Center, Harbin First Hospital, Harbin, Heilongjiang 150001, P.R. China, Department of Orthopedics, The Second Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: September 19, 2018 https://doi.org/10.3892/etm.2018.6770
Pages: 4737-4744

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Abstract

Osteoarthritis is a degenerative disease that often causes patients to experience joint pain and deformity. It has been demonstrated that tumor necrosis factor (TNF)‑α is associated with the progression of osteoarthritis; however, to the best of our knowledge, the mechanisms by which TNF‑α simulates the progression of osteoarthritis and the signaling pathway(s) it influences remain unknown. Therefore, the aim of the present study was to investigate the therapeutic effects of TNF‑α inhibitor in an iodoacetate‑induced rat model of osteoarthritis and identify its potential mechanisms of action. Western blotting, ELISA and histological analyses were performed to assess the effects of the TNF‑α inhibitor on osteoarthritis. The effects of TNF‑α and phosphoinositide 3‑kinase (PI3K) inhibition on synovial fibroblasts isolated from rats with osteoarthritis were tested in vitro. Furthermore, the expression of various inflammatory cytokines and the PI3K/protein kinase B (AKT) signaling pathway were assessed in vitro. The results indicated that the inflammatory factors TNF‑α, interleukin (IL)‑1β, IL‑17a and IL‑8 were upregulated in synovial fibroblasts taken from rats with osteoarthritis compared with normal rats. By contrast, TNF‑α inhibition downregulated IL‑1β, IL‑17a and IL‑8 expression in synovial fibroblasts in vitro. The PI3K/AKT pathway was also upregulated in synovial fibroblasts harvested from rats with osteoarthritis compared with that in normal rats. It was demonstrated that treatment with the TNF‑α inhibitor downregulated the serum and protein levels of IL‑1β, IL‑17a and IL‑8 in rats with osteoarthritis. Furthermore, treatment with the TNF‑α inhibitor also decreased matrix metalloproteinase (MMP)‑3, MMP‑9, vascular endothelial growth factor and ADAMTS4 expression in synovial fibroblasts isolated from rats with osteoarthritis. Treatment with the TNF‑α inhibitor also inhibited the PI3K/AKT pathway in synovial fibroblasts isolated from rats with osteoarthritis. Treatment with the PI3K inhibitor ameliorated TNF‑α‑induced increases in IL‑1β, IL‑17a and IL‑8 expression in synovial fibroblasts isolated from rats with osteoarthritis. Furthermore, treatment with the TNF‑α inhibitor decreased inflammation, as well as joint and cartilage destruction in vivo. Taken together, the results of the present study indicate that TNF‑α inhibition may downregulate the expression of inflammatory factors in synovial fibroblasts, suggesting that TNF‑α inhibition may be a novel method for treating osteoarthritis by downregulating the PI3K/AKT signaling pathway.

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