Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/ijms22020703
Keywords
intervertebral disc; extracellular matrix; disc cell molecular biology; multifactorial cell stimulation; intervertebral disc degeneration; regenerative medicine; multiscale modeling; computational multiphysics; computational systems biology
Funding
- German Research Foundation (DFG) via the scholarship Forschungsstipendium [387071423]
- Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCHCREATE-INNOVATE - European Union
- Greek national funds [T1EDK-02829]
- Swiss National Science Foundation [SNF PP00P2_163678/1]
- Spanish Ministry of Science and Innovation [HOLOA-DPI2016-80283-C2-1-R, RYC-2015-18888]
- European Commission (Disc4All-H2020-MSCA-ITN-ETN-2020) [955735]
- MRC [MR/P026796/1] Funding Source: UKRI
- Marie Curie Actions (MSCA) [955735] Funding Source: Marie Curie Actions (MSCA)
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Degenerative changes in the intervertebral disc are a major risk factor for low back pain, with accelerated progression in some individuals as they age. Understanding the disease requires identifying key regulatory processes at various levels, from cells to organs. Experimental research and computational modeling have contributed significantly to our understanding of cell signaling pathways and complex interactions within the intervertebral disc.
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.
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