An in‐depth analysis of the immunomodulatory mechanisms of intervertebral disc degeneration

Abstract

Intervertebral disc degeneration (IVDD) is the pathological basis of disc herniation, spinal stenosis, and other related diseases, and the lower back pain it produces lays a heavy financial burden on individuals and society. Thus, it is essential to comprehend IVDD's pathophysiology. Numerous factors, such as inflammatory factors, oxidative stress, apoptosis, matrix metalloproteinases, are linked to IVDD pathogenesis.Despite the fact that many researches has provided explanations for the pathophysiology of IVDD, these studies are typically singular, restricted, and isolated, expound only on one or two components, and do not systematically analyze and summarize the numerous influencing elements. In addition, we discovered that the incidence of many chronic diseases in the field of orthopedics may be thoroughly and systematically defined in terms of immunological systems. In order to provide a theoretical foundation for an in-depth understanding of the pathological process of IVDD and the formulation of more effective prevention and treatment measures, this review provides a comprehensive and systematic account of the pathogenesis of IVDD from the physical to the molecular barriers of the intervertebral disc, from the nucleus pulposus tissue to the cellular to the immune-molecular level.

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

“…Through bioinformatic data analysis, we clarified that senescence and apoptosis signaling pathways play an important role in the development of IVDD, and based on our group's previous research and literature, we believe that NPCs are important cells in IVDD. 3,14,30,31 Therefore, we hypothesize that SP1, CASP3, VEGFA, and IL- S7; Figure 9B). We can see from the WB results that CASP3 is different in the model and control groups in protein levels, but the statistical significance is less significant.…”

“…IVDD is caused by degeneration and hyalinization of the fibrous ring tissue, water loss in the nucleus pulposus tissue, increased immune cell infiltration, and inflammatory mediators 33 . The majority of current thinking holds that CS and immunological inflammation are inextricably related to the numerous clinical processes associated with IVDD 3,14 . Specifically, CS may accelerate disease progression in IVDD by activating immune‐inflammatory responses through ROS, promoting intervertebral disc ECM breakdown, and apoptosis, as well as by inducing oxidative stress and autophagy 14 .…”

“…The immune system response and inflammation are now widely recognized as important drivers of IVDD pathogenesis and progression 3,44,45 . We know that under normal physiological conditions, the nucleus pulposus is the largest immune‐privileged tissue in the body, due to the fact that it is covered by the outer layer of the AF and the upper and lower parts of the CEP in a special enclosed space 46,47 .…”

“…Intervertebral disc degeneration (IVDD) is a musculoskeletal degenerative condition associated with aging that lowers people's quality of life and places a greater financial burden on society 1 . The pathogenesis of IVDD is now thought to be primarily caused by cellular senescence (CS) or death of nucleus pulposus cells (NPCs), an imbalance of extracellular matrix (ECM) formation and degradation, and inflammation, oxidative stress, but the precise pathophysiology is not entirely understood 2,3 . Therefore, it is necessary to explore the pathogenesis of IVDD.…”

Exploring the pharmacological mechanism of Duhuo Jisheng Decoction in treating intervertebral disc degeneration based on network pharmacology

“…[40] Many inflammatory factors, including IL-12, TGF-a, IL6, IL1β, IL-21, and IL-23, cause CD4 + Th17 cells to produce IL-17A, which activates downstream signaling pathways leading to IVDD. [41,42] IL-17A alone is not enough to strongly activate the downstream NF-B signaling pathway, according to a search of the KEGG signaling pathway database and literature. As a result, IL-17A and other cytokines like TNF-α and IL-1β costimulate the NF-B signaling pathway and improve the stability of pro-inflammatory cytokine and chemokine gene expression.…”