Suramin attenuates intervertebral disc degeneration by inhibiting NF-κB signalling pathway

Bone & Joint Research

article

Zi-Miao Liu¹  Cheng-Chang Lu²  Po-Chih Shen¹  Shih-Hsiang Chou¹  Chia-Lung Shih¹  Jian-Chih Chen¹  Yin Chun Tien¹ 

[1] Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University;Department of Orthopedics, Faculty of Medical School, College of Medicine, Kaohsiung Medical University

关键词: Suramin;    Intervertebral disc degeneration;    NF-κB;    Apoptosis;    Inflammation;    intervertebral disc degeneration;    western blotting;    apoptosis;    cytokines;    IL-8;    aggrecan;    MMP-13;    matrix metalloproteinases-3;    ADAMTS-5;    ADAMTS-4;   

DOI  :  10.1302/2046-3758.108.BJR-2020-0041.R3

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsInterleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism.MethodsPorcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.ResultsSuramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments.ConclusionSuramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells.

【 授权许可】

CC BY-NC