Development, Pathogenesis, and Regeneration of the Intervertebral Disc: Current and Future Insights Spanning Traditional to Omics Methods

Abstract

The intervertebral disc (IVD) is the fibrocartilaginous joint located between each vertebral body that confers flexibility and weight bearing capabilities to the spine. The IVD plays an important role in absorbing shock and stress applied to the spine, which helps to protect not only the vertebral bones, but also the brain and the rest of the central nervous system. Degeneration of the IVD is correlated with back pain, which can be debilitating and severely affects quality of life. Indeed, back pain results in substantial socioeconomic losses and healthcare costs globally each year, with about 85% of the world population experiencing back pain at some point in their lifetimes. Currently, therapeutic strategies for treating IVD degeneration are limited, and as such, there is great interest in advancing treatments for back pain. Ideally, treatments for back pain would restore native structure and thereby function to the degenerated IVD. However, the complex developmental origin and tissue composition of the IVD along with the avascular nature of the mature disc makes regeneration of the IVD a uniquely challenging task. Investigators across the field of IVD research have been working to elucidate the mechanisms behind the formation of this multifaceted structure, which may identify new therapeutic targets and inform development of novel regenerative strategies. This review summarizes current knowledge base on IVD development, degeneration, and regenerative strategies taken from traditional genetic approaches and omics studies and discusses the future landscape of investigations in IVD research and advancement of clinical therapies.

Glis1 and oxaloacetate in nucleus pulposus stromal cell somatic reprogramming and survival

“…Cells in the IVD and FAT are of mesoderm origin, yet terminal differentiation follows different paths. Advanced omics technologies in IVD research allow for transcriptome profiling at a single and cell population average level ( Hickman et al, 2022 ). Despite the lack of natural signaling cues in monolayer culture, transcripts of the three cell lines (NP, AF, and FAT) in early 2D culture reflect their mesoderm origin alongside their lineage profile through overlapping and distinct molecular signatures.…”

Platelet-derived extracellular vesicles ameliorate intervertebral disc degeneration by alleviating mitochondrial dysfunction

“…The impairment of mitochondrial function is strongly associated with degenerative diseases [ [60] , [61] , [62] ]. Inflammatory degeneration is exacerbated because of an insufficient ATP supply when mitochondria are impaired [ 63 , 64 ]. Fen et al.…”

Red Light-Mediated Photoredox Catalysis Triggers Nitric Oxide Release for Treatment of Cutibacterium Acne Induced Intervertebral Disc Degeneration

“…Low back pain (LBP) is a common health issue with a high lifetime prevalence (∼80%), in which ∼10% of patients suffer from chronic low back pain (CLBP) that can lead to disability . Therefore, CLBP brings great challenges to personal health and social medical care, while intervertebral disc degeneration (IVDD) and Modic changes are recognized as an important cause of CLBP. , The incidence of IVDD can be attributed to genetics, trauma, stress, infection, etc., while Modic changes are closely associated with IVDD, which is manifested by abnormal signals of cartilage and bone end plates . Modic changes (MCs) are a type of bone marrow lesion of the vertebrae adjacent to degenerated discs.…”