Suramin attenuates intervertebral disc degeneration by inhibiting NF-κB signalling pathway
| العنوان: | Suramin attenuates intervertebral disc degeneration by inhibiting NF-κB signalling pathway |
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| المؤلفون: | Yin Chun Tien, Cheng-Chang Lu, Zi-Miao Liu, Jian-Chih Chen, Chia-Lung Shih, Po-Chih Shen, Shih-Hsiang Chou |
| المصدر: | Bone & Joint Research, Vol 10, Iss 8, Pp 498-513 (2021) Bone & Joint Research |
| بيانات النشر: | The British Editorial Society of Bone & Joint Surgery, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | mmp-13, Suramin, Inflammation, Degeneration (medical), Diseases of the musculoskeletal system, Arthroplasty, adamts-4, chemistry.chemical_compound, adamts-5, matrix metalloproteinases-3, il-8, medicine, Orthopedics and Sports Medicine, Interleukin 8, nf-κb, suramin, Hip, intervertebral disc degeneration, western blotting, business.industry, apoptosis, Interleukin, NF-κB, Intervertebral disc, Reverse Hybrid, cytokines, medicine.anatomical_structure, chemistry, RC925-935, Apoptosis, inflammation, Cancer research, Surgery, medicine.symptom, aggrecan, business, medicine.drug |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2046-3758 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f8b59f375c69694a9dec706f93ada36e https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.108.BJR-2020-0041.R3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f8b59f375c69694a9dec706f93ada36e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20463758 |
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