Multiscale regulation of the intervertebral disc: achievements in experimental, in silico, and regenerative research

Baumgartner, Laura; Wuertz-Kozak, Karin; Le Maitre, Christine L.; Wignall, Francis; Richardson, Stephen M.; Hoyland, Judith; Ruiz Wills, Carlos; González Ballester, Miguel Ángel, 1973-; Neidlin, Michael; Alexopoulos, Leonidas G.; Noailly, Jérôme

doi:http://dx.doi.org/10.3390/ijms22020703

Multiscale regulation of the intervertebral disc: achievements in experimental, in silico, and regenerative research

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Baumgartner L, Wuertz-Kozak K, Le Maitre CL, Wignall F, Richardson SM, Hoyland J, Ruiz Wills C, González Ballester MA, Neidlin M, Alexopoulos LG, Noailly J. Multiscale regulation of the intervertebral disc: achievements in experimental, in silico, and regenerative research. Int J Mol Sci. 2021 Jan 12;22(2):703. DOI: 10.3390/ijms22020703

Abstract

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