Defects in intervertebral disc and spine during development, degeneration, and pain: New research directions for disc regeneration and therapy

Abstract

Intervertebral discs are cartilaginous joints present between vertebrae. The centers of the intervertebral discs consist of a gelatinous nucleus pulposus derived from the embryonic notochord. With age or injury, intervertebral discs may degenerate, causing neurological symptoms including back pain, which affects millions of people worldwide. Back pain is a multifactorial disorder, and disc degeneration is one of the primary contributing factors. Recent studies in mice have identified the key molecules involved in the formation of intervertebral discs. Several of these key molecules including sonic hedgehog and Brachyury are not only expressed by notochord during development, but are also expressed by neonatal mouse nucleus pulposus cells, and are crucial for postnatal disc maintenance. These findings suggest that intrinsic signals in each disc may maintain the nucleus pulposus microenvironment. However, since expression of these developmental signals declines with age and degeneration, disc degeneration may be related to the loss of these intrinsic signals. In addition, findings from mouse and other mammalian models have identified similarities between the patterning capabilities of the embryonic notochord and young nucleus pulposus cells, suggesting that mouse is a suitable model system to understand disc development and aging. Future research aimed at understanding the upstream regulators of these developmental signals and the modes by which they regulate disc growth and maintenance will likely provide mechanistic insights into disc growth and aging. Further, such findings will likely provide insights relevant to the development of effective therapies for treatment of back pain and reversing the disc degenerative process.

Activation of SIRT1 promotes cartilage differentiation and reduces apoptosis of nucleus pulposus mesenchymal stem cells via the MCP1/CCR2 axis in subjects with intervertebral disc degeneration

“…MScs reduce stress-mediated NP cell apoptosis, thus relieving the severity of Idd (5). currently, Idd, which is associated with the accumulation of injuries and aging, is a health threat to millions of individuals worldwide (6). In this context, biomarkers for early stage diagnosis and novel therapeutic strategies for Idd are urgently needed.…”

Transcriptomics Study to Determine the Molecular Mechanism by which sIL-13Rα2-Fc Inhibits Caudal Intervertebral Disc Degeneration in Rats

“…One of the characteristics of intervertebral disc degeneration is the injury of and formation of lesions in the peripheral tissue, which are difficult to heal. When pathological changes occur in the annulus fibrosus or cartilage endplate, it also means that local tissues have been damaged or have undergone an inflammatory response [2,4]. The structural change in the intervertebral disc tissue is a sign of impaired intervertebral disc function, and such a structural change is permanent [20].…”

“…Intervertebral disc degeneration is the underlying basic pathological process of a series of spinal degenerative diseases (such as disc herniation, spinal canal stenosis, spondylolisthesis, spinal instability, and neuropathy) [ 1 ]; however, the specific pathophysiological mechanism involved remains unclear. Most scholars believe that the main mechanisms of intervertebral disc degeneration include tissue fibrosis, intervertebral disc cartilage endplate degeneration, a decrease in the number of bone marrow cells (either through increased apoptosis and autophagy or by decreased proliferation), local effects (such as oxidative stress and vascular hyperplasia), decomposition of the extracellular matrix, and the effects of inflammatory cytokines [ 2 – 4 ]. Because of the changes in the rates of the synthesis and decomposition of the extracellular matrix in degenerative discs, there are increased levels of type I collagen and decreased levels of type II collagen, and proteoglycan synthesis is reduced.…”

Silencing of Long Non-coding RNA NEAT1 Upregulates miR-195a to Attenuate Intervertebral Disk Degeneration via the BAX/BAK Pathway

“…Long-chain non-coding RNA (LncRNA) has been proved to be involved in regulating various biological processes. Meanwhile, IVDD is a complex process involving genetic factors, biomechanics, apoptosis, and other internal and external factors that ultimately lead to pathological changes ( Dowdell et al, 2017 ; Mohanty and Dahia, 2019 ). Differentially expressed long non-coding RNAs (lncRNAs) in intervertebral disk tissues play a vital role in the progression of IVDD by regulating the expression of target genes to affect the proliferation and apoptosis of nucleus pulposus (NP) cells, changes in the ECM, and other physiological processes ( Chen W.K.…”