SDF‑1/CXCR4 axis induces apoptosis of human degenerative nucleus pulposus cells via the NF‑κB pathway

Liu,Zongchao; Ma,Chuan; Shen,Jieliang; Wang,Dawu; Hao,Jie; Hu,Zhenming

doi:10.3892/mmr.2016.5341

SDF‑1/CXCR4 axis induces apoptosis of human degenerative nucleus pulposus cells via the NF‑κB pathway

Authors:
- Zongchao Liu
- Chuan Ma
- Jieliang Shen
- Dawu Wang
- Jie Hao
- Zhenming Hu
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Affiliations: Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Orthopedic Surgery, The Traditional Chinese Medicine Affiliated Hospital of Sichuan Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: May 24, 2016 https://doi.org/10.3892/mmr.2016.5341
Pages: 783-789
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intervertebral disc degeneration (IVDD) is a major cause of lower back pain, and increased cell apoptosis is a key characteristic of IVDD. The present study aimed to investigate the effects and mechanism of the stromal cell‑derived factor‑1 (SDF‑1)/C‑X‑C motif chemokine receptor 4 (CXCR4) axis on apoptosis in human degenerative nucleus pulposus cells (NPCs). The expression levels of SDF‑1 and CXCR4 in human intervertebral discs (IVD) were determined using immunohistochemistry and western blot analysis. Apoptosis of primary cultured NPCs was quantified by Annexin V/propidium iodide staining following stimulation with SDF‑1 and knockdown of CXCR4 using small interfering RNA (siRNA). The association with the nuclear factor‑κB (NF‑κB) signaling pathway was investigated using CXCR4‑siRNA and NF‑κB inhibitor, pyrrolidine dithiocarbamate (PDTC), treatment. The results demonstrated that SDF‑1 and its receptor, CXCR4, were upregulated in degenerative IVD samples compared with normal samples. Stimulation with SDF‑1 increased the level of apoptosis in cultured NPCs, and conversely, the apoptosis level was suppressed post‑transfection with CXCR4 siRNA compared with SDF‑1 stimulation alone. Furthermore, SDF‑1 treatment increased the level of phosphorylated NF‑κB subunit P65, which was downregulated following CXCR4 siRNA and PDTC treatment. In addition, CXCR4 siRNA and PDTC inhibited the nuclear translocation of P65, which was induced by SDF‑1. Taken together, SDF‑1‑mediated apoptosis was suppressed by NF‑κB inhibition using PDTC. In conclusion, the SDF‑1/CXCR4 axis promoted cell apoptosis in human degenerative NPCs via the NF‑κB pathway, thus suggesting that SDF‑1/CXCR signaling may be a therapeutic target for the treatment of degenerative IVD diseases.

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