Oncotarget

Research Papers: Pathology:

Epoxyeicosanoids prevent intervertebral disc degeneration in vitro and in vivo

Jing Li, Hanfeng Guan, Huiyong Liu, Libo Zhao, Li Li, Yong Zhang, Peng Tan, Baoguo Mi and Feng Li _

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Oncotarget. 2017; 8:3781-3797. https://doi.org/10.18632/oncotarget.14389

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Abstract

Jing Li1,*, Hanfeng Guan1,*, Huiyong Liu1, Libo Zhao1, Li Li2, Yong Zhang1, Peng Tan1, Baoguo Mi1 and Feng Li1

1 Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

2 Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

* These authors have contributed equally to this work

Correspondence to:

Feng Li, email:

Keywords: epoxyeicosatrienoic acids, intervertebral disc degeneration, nucleus pulposus cells, NF-κB, Pathology Section

Received: June 27, 2016 Accepted: December 16, 2016 Published: December 30, 2016

Abstract

Intervertebral disc (IVD) degeneration is considered a common cause of low back pain. In the degenerating IVD, the production of pro-inflammatory cytokines, including IL-1 and TNF-α, progressively increases, contributing to the degenerative process. Epoxyeicosatrienoic acids (EETs), synthesized from arachidonic acid by cytochrome P450 enzymes, act as autocrine and paracrine effectors in regulating inflammation, cardiovascular functions, and angiogenesis. EETs were shown to be especially potent promoters of tissue regeneration. Considering their anti-inflammatory and anti-catabolic potential, we investigated whether EETs can influence IVD degeneration. We found that 14,15-EET protected rat nucleus pulposus (NP) cells against death induced by treatment with H2O2and TNF-α in vitro. At the molecular level, 14,15-EET significantly inhibited the NF-κB pathway, which plays essential roles in the degeneration and survival of NP cells. As a result, 14,15-EET efficiently prevented the matrix remodeling response of NP cells to TNF-α. Using a needle-punctured rat tail model, the influence of 14,15-EET on IVD degeneration in vivo was evaluated using radiographs, magnetic resonance images (MRI), and histological analysis. We observed that 14,15-EET prevented IVD degeneration. Our findings demonstrated that 14,15-EET can enhance the survival of NP cells and inhibit IVD degeneration. The EET pathway may be a novel therapeutic target against IVD degeneration.


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