Immuno-Modulatory Effects of Intervertebral Disc Cells

Abstract

Low back pain is a highly prevalent, chronic, and costly medical condition predominantly triggered by intervertebral disc degeneration (IDD). IDD is often caused by structural and biochemical changes in intervertebral discs (IVD) that prompt a pathologic shift from an anabolic to catabolic state, affecting extracellular matrix (ECM) production, enzyme generation, cytokine and chemokine production, neurotrophic and angiogenic factor production. The IVD is an immune-privileged organ. However, during degeneration immune cells and inflammatory factors can infiltrate through defects in the cartilage endplate and annulus fibrosus fissures, further accelerating the catabolic environment. Remarkably, though, catabolic ECM disruption also occurs in the absence of immune cell infiltration, largely due to native disc cell production of catabolic enzymes and cytokines. An unbalanced metabolism could be induced by many different factors, including a harsh microenvironment, biomechanical cues, genetics, and infection. The complex, multifactorial nature of IDD brings the challenge of identifying key factors which initiate the degenerative cascade, eventually leading to back pain. These factors are often investigated through methods including animal models, 3D cell culture, bioreactors, and computational models. However, the crosstalk between the IVD, immune system, and shifted metabolism is frequently misconstrued, often with the assumption that the presence of cytokines and chemokines is synonymous to inflammation or an immune response, which is not true for the intact disc. Therefore, this review will tackle immunomodulatory and IVD cell roles in IDD, clarifying the differences between cellular involvements and implications for therapeutic development and assessing models used to explore inflammatory or catabolic IVD environments.

No evidence of association between either Modic change or disc degeneration and five circulating inflammatory proteins

“…While systemic levels of the five inflammatory proteins tested were not associated with IVDD and MC in this study, there is compelling evidence that local inflammatory factors produce changes in both MC (BM) 21,72 and IVDD (disc tissue) 73,74 . BM hosts different immune cell types, which naturally produce these cytokines, 75 and BM vascularization could lead to the rapid translocation of BM‐produced cytokines to the blood flow leading to potential biomarkers of BM pathology, as shown for different BM conditions 76,77 .…”

Predicting Gene Disease Associations With Knowledge Graph Embeddings for Diseases With Curtailed Information

“…Finally, we used the selected prediction model with best parametrization to predict GDAs for IDD. IDD is one of the main causes of low back pain (LBP), the largest cause of morbidity worldwide affecting 80% of people from Western countries during their lifetime (47). IDD consists of the gradual deterioration of the intervertebral disc (IVD) in which the content of collagen and glycosaminoglycan decreases, and it becomes more dehydrated and fibrotic.…”

Cartilaginous endplates: A comprehensive review on a neglected structure in intervertebral disc research

“…Other methods suggested include enzymatic treatment, such as trypsin or hyaluronidase, to remove large proteoglycans from the CEP 209 . However, chemical injection with enzymes is also used to induce degeneration in animal models 180 . Therefore, the use of enzymes for CEP therapies should be strictly restricted to the CEP.…”