Baumgartner, LauraWuertz-Kozak, KarinLe Maitre, Christine L.Wignall, FrancisRichardson, Stephen M.Hoyland, JudithRuiz Wills, CarlosGonzález Ballester, Miguel Ángel, 1973-Neidlin, MichaelAlexopoulos, Leonidas G.Noailly, Jérôme2021-03-102021-03-102021Baumgartner 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/ijms220207031661-6596http://hdl.handle.net/10230/46714Intervertebral 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 therapiesapplication/pdfeng© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/ijms22020703Intervertebral discExtracellular matrixDisc cell molecular biologyMultifactorial cell stimulationIntervertebral disc degenerationRegenerative medicineMultiscale modelingComputational multiphysicsComputational systems biologyinfo:eu-repo/semantics/openAccess