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椎间盘髓核细胞网络建模

Nucleus pulposus cell network modelling in the intervertebral disc.

作者信息

Tseranidou Sofia, Segarra-Queralt Maria, Chemorion Francis Kiptengwer, Le Maitre Christine Lyn, Piñero Janet, Noailly Jérôme

机构信息

Department of Engineering, Universitat Pompeu Fabra, Barcelona, Spain.

Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, United Kingdom.

出版信息

NPJ Syst Biol Appl. 2025 Jan 31;11(1):13. doi: 10.1038/s41540-024-00479-6.

Abstract

Intervertebral disc degeneration (IDD) results from an imbalance between anabolic and catabolic processes in the extracellular matrix (ECM). Due to complex biochemical interactions, a comprehensive understanding is needed. This study presents a regulatory network model (RNM) for nucleus pulposus cells (NPC), representing normal intervertebral disc (IVD) conditions. The RNM includes 33 proteins, and 153 interactions based on literature, incorporating key NPC regulatory mechanisms. A semi-quantitative approach calculates the basal steady state, accurately reflecting normal NPC activity. Model validation through published studies replicated pro-catabolic and pro-anabolic shifts, emphasizing the roles of transforming growth factor beta (TGF-β) and interleukin-1 receptor antagonist (IL-1Ra) in ECM regulation. This IVD RNM is a valuable tool for predicting IDD progression, offering insights into ECM degradation mechanisms and guiding experimental research on IVD health and degeneration.

摘要

椎间盘退变(IDD)是由细胞外基质(ECM)合成代谢和分解代谢过程失衡所致。由于存在复杂的生化相互作用,因此需要全面了解。本研究提出了一种用于髓核细胞(NPC)的调控网络模型(RNM),该模型代表正常椎间盘(IVD)状况。该RNM包括33种蛋白质和基于文献的153种相互作用,纳入了关键的NPC调控机制。一种半定量方法计算基础稳态,准确反映正常NPC活性。通过已发表的研究进行模型验证,重现了促分解代谢和促合成代谢转变,强调了转化生长因子β(TGF-β)和白细胞介素-1受体拮抗剂(IL-1Ra)在ECM调节中的作用。这种IVD RNM是预测IDD进展的宝贵工具,为ECM降解机制提供见解,并指导关于IVD健康和退变的实验研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a6/11785752/00dca0207f3d/41540_2024_479_Fig1_HTML.jpg

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