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.
Highlights
Introduction ditions of the Creative CommonsAt-The intervertebral disc (IVD) is a major mechanical load-bearing organ and is responsible for the functional articulation of the spine
Notch signaling in the Intervertebral disc (IVD) was activated by hypoxia [237] and pro-inflammatory cytokine exposure [235], thereby activating nucleus pulposus (NP) and annulus fibrosus (AF) cell proliferation [236,237], inhibiting NP cell apoptosis promoted by tumor necrosis factor α (TNF-α) [236] and modulating the expression of anabolic and catabolic genes [238]
This review provides an integrative view of the current knowledge about the nondegenerated and degenerated IVD at the tissue, cell, and molecular levels and of current disc regeneration strategies
Summary
The biochemistry and the ultrastructure of the intervertebral intervertebral disc ECM. I and II), and PG, the relative contents and tissues are water, collagen PGPG is is present ininthe to the present theinterlamellar interlamellarspace, space,along alongwith withsmall smallamounts amountsof of elastic elastic fibers fibers and and other other types types of of fibrils fibrils [43]. It has has been been demonstrated demonstrated that that the the turnover turnover rate rate of of collagen and aggrecan in the is relatively slow due to long half-lives, i.e., around collagen and aggrecan in the IVD is relatively slow due to long half-lives, i.e., around 95 and and 12.
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