Expression and effects of leukemia inhibitory factor on nucleus pulposus degeneration

Xiao,Qiang; Zeng,Ji‑Huan; Zhou,Hao; Qiu,Quan‑He; Ke,Bo; Deng,Liang; Hu,Zhen‑Ming; Roh,Jeffrey; Dai,Min

doi:10.3892/mmr.2019.9874

Expression and effects of leukemia inhibitory factor on nucleus pulposus degeneration

Authors:
- Qiang Xiao
- Ji‑Huan Zeng
- Hao Zhou
- Quan‑He Qiu
- Bo Ke
- Liang Deng
- Zhen‑Ming Hu
- Jeffrey Roh
- Min Dai
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Affiliations: Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Orthopaedics, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China, Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Orthopaedics, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330029, P.R. China, Department of Hematopathology, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China, Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA 98122, USA, Department of Orthopaedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: January 17, 2019 https://doi.org/10.3892/mmr.2019.9874
Pages: 2377-2385

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Abstract

Leukemia inhibitory factor (LIF) is a multifunctional cytokine. The present study aimed to determine the expression and effects of LIF on nucleus pulposus generation. Degenerated nucleus pulposus samples were obtained from animal models and patients with lumbar intervertebral disc herniation. Degradation scores of intervertebral discs were evaluated via magnetic resonance imaging (MRI) and histology, and the protein expression levels of LIF were detected. Furthermore, cultured primary human degenerated nucleus pulposus cells (DNPCs) were stimulated with various concentrations of recombinant human LIF protein (rhLIF), and aggrecan and collagen type II α1 (COL2α1) protein expression levels were detected by western blotting. In addition, aggrecan expression was determined by toluidine blue staining. The effects of rhLIF on proliferation and apoptosis of DNPCs were evaluated by Cell Counting Kit‑8 and flow cytometry, respectively. The results revealed that the degradation scores of intervertebral discs were significantly associated with modeling time, as determined by MRI and histology. In addition, the protein expression levels of LIF were initially increased in patients with lumbar disc herniation and in rabbit models, particularly in the 2‑week modeling group; however, its expression decreased with the progression of disc degeneration. Notably, LIF expression in each modeling group was higher than that in the control and 0 week modeling group. The in vitro study revealed that the protein expression levels of aggrecan and COL2α1 were significantly increased in response to rhLIF, in a dose‑dependent manner, and statistical differences were identified between the treatment groups and control group. The results of toluidine blue staining were consistent with this finding. Although rhLIF had no effect on proliferation, it inhibited apoptosis of DNPCs in a concentration‑dependent manner. In conclusion, LIF was upregulated during the process of intervertebral disc degeneration, and may promote the expression of extracellular matrix components. It may also be hypothesized that LIF acts as a potential protective factor by inhibiting apoptosis of DNPCs without affecting cell proliferation.

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