Baumgartner Laura, Wuertz-Kozak Karin, Le Maitre Christine L, Wignall Francis, Richardson Stephen M, Hoyland Judith, Ruiz Wills Carlos, González Ballester Miguel A, Neidlin Michael, Alexopoulos Leonidas G, Noailly Jérôme
BCN MedTech, Department of Information and Communication Technologies, Universitat Pompeu Fabra, 08018 Barcelona, Spain.
Department of Biomedical Engineering, Rochester Institute of Technology (RIT), Rochester, NY 14623, USA.
Int J Mol Sci. 2021 Jan 12;22(2):703. doi: 10.3390/ijms22020703.
Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations' processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.
椎间盘（IVD）退变是腰痛的主要危险因素。它被定义为IVD结构和功能的逐渐丧失，由于IVD承受的机械负荷极高，导致严重损伤且治疗选择受限。IVD的退行性变化通常随年龄增长而增加，但在某些个体中会加速。为了了解这种疾病的起始和进展，至关重要的是确定在健康和疾病状态下，跨越细胞、组织和器官水平的关键自上而下和自下而上的调控过程。由于对实验研究的不懈探索，对详细细胞信号通路及其对基质周转影响的理解有了显著提高。同样，计算机模拟研究对全面理解IVD内的时空效应以及复杂的多因素相互作用也做出了重大贡献。随着生物材料研究取得重要成果，在过去几年中提出了多种有前景的再生治疗方法。本综述对当前有关（1）健康和疾病状态下IVD的多尺度功能和调控、（2）可能的再生策略以及（3）最终应支持先进疗法开发的计算机模拟模型的知识进行了综合分析。
