Oxidized low density lipoprotein facilitates tumor necrosis factor‑α mediated chondrocyte death via autophagy pathway

Shen,Pengcheng; Zhu,Yu; Zhu,Lifan; Weng,Fengbiao; Li,Xiaolin; Xu,Yaozeng

doi:10.3892/mmr.2017.7786

Oxidized low density lipoprotein facilitates tumor necrosis factor‑α mediated chondrocyte death via autophagy pathway

Authors:
- Pengcheng Shen
- Yu Zhu
- Lifan Zhu
- Fengbiao Weng
- Xiaolin Li
- Yaozeng Xu
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Affiliations: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Orthopaedics, Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215100, P.R. China, Department of Orthopaedics, The First People's Hospital of Wujiang District, Suzhou, Jiangsu 215200, P.R. China, Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, P.R. China
Published online on: October 13, 2017 https://doi.org/10.3892/mmr.2017.7786
Pages: 9449-9456
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

We aimed to investigate the role of oxidized low density lipoprotein (ox‑LDL) in tumor necrosis factor‑α (TNF‑α) mediated chondrocyte death and explore the mechanisms. Ten osteoarthritis (OA) and normal control cartilage tissue and synovial fluid (SF) samples were collected, and the expression of lectin‑like ox‑LDL receptor‑1 (LOX‑1) and ox‑LDL level was examined by real time quantitative PCR and enzyme‑linked immunosorbent assay (ELISA). An in vitro chondrocyte model was established by the introduction of TNF‑α and ox‑LDL, cell death was analyzed by trypan blue assay and the mechanisms were explored based on the apoptosis related pathway and autophagy pathway. Significantly increased ox‑LDL level (70.30±17.83 vs. 37.22±19.97, P<0.05) in SF sample and LOX‑1 expression level (0.51±0.10 vs. 0.32±0.04, P<0.05) in cartilage tissue was found in OA patients compared to those corresponding samples from control subjects. Ox‑LDL could facilitate TNF‑α mediated chondrocyte death and this effect could be blocked by LOX‑1 antibody neutralization. Autophagy inhibition by 3‑MA and Atg‑5 siRNA could reverse the cell death effect mediated by TNF‑α and ox‑LDL co‑treatment on chondrocytes. Oxidized low density lipoprotein facilitates tumor necrosis factor‑α mediated chondrocyte death via its interaction with LOX‑1, and autophagy is involved in the mechanisms.

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