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

Zi-Miao Liu; Cheng-Chang Lu; Po-Chih Shen; Shih-Hsiang Chou; Chia-Lung Shih; Jian-Chih Chen; Yin Chun Tien

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

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

Bone Joint Res. 2021 Aug;10(8):498-513. doi: 10.1302/2046-3758.108.BJR-2020-0041.R3.

Authors

Zi-Miao Liu¹, Cheng-Chang Lu², Po-Chih Shen¹, Shih-Hsiang Chou¹, Chia-Lung Shih¹, Jian-Chih Chen¹, Yin Chun Tien^{1

2}

Affiliations

¹ Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
² Department of Orthopedics, Faculty of Medical School, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

PMID: 34372688
PMCID: PMC8414441
DOI: 10.1302/2046-3758.108.BJR-2020-0041.R3

Abstract

Aims: Interleukin (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.

Methods: Porcine 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.

Results: Suramin 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.

Conclusion: Suramin 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. Cite this article: Bone Joint Res 2021;10(8):498-513.

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