From structure to therapy: the critical influence of cartilaginous endplates and microvascular network on intervertebral disc degeneration

Abstract

The intervertebral disc (IVD) is the largest avascular structure in the human body. The cartilaginous endplate (CEP) is a layer of translucent cartilage located at the upper and lower edges of the vertebral bodies. On one hand, CEPs endure pressure from within the IVD and the tensile and shear forces of the annulus fibrosus, promoting uniform distribution of compressive loads on the vertebral bodies. On the other hand, microvascular diffusion channels within the CEP serve as the primary routes for nutrient supply to the IVD and the transport of metabolic waste. Degenerated CEP, characterized by increased stiffness, decreased permeability, and reduced water content, impairs substance transport and mechanical response within the IVD, ultimately leading to intervertebral disc degeneration (IDD). Insufficient nutrition of the IVD has long been considered the initiating factor of IDD, with CEP degeneration regarded as an early contributing factor. Additionally, CEP degeneration is frequently accompanied by Modic changes, which are common manifestations in the progression of IDD. Therefore, this paper comprehensively reviews the structure and physiological functions of CEP and its role in the cascade of IDD, exploring the intrinsic relationship between CEP degeneration and Modic changes from various perspectives. Furthermore, we summarize recent potential therapeutic approaches targeting CEP to delay IDD, offering new insights into the pathological mechanisms and regenerative repair strategies for IDD.

Keywords: Modic changes; cartilage endplate; intervertebral disc degeneration; microvessels; nutrient diffusion.

FIGURE 1

(A) Healthy IVD: In a healthy IVD, AF collagen fibers enter the bottom of the CEP parallel to the bone. The collagen fibers of NP partially permeate the CEP. The CEP is penetrated by vascular plexus from the vertebral bone cancellous, in which the epiphyseal artery and the trophic artery end branch formed a dense capillary network. (B) Degenerative IVD: The degenerative CEP has reduced thickness, calcification and fibrosis of the inner and outer layers leading to apoptosis, in addition to progressive atrophy of the vascular bed within the CEP, hardening of the adjacent bone endplate and progressive stripping from the CEP. At the same time, the binding between NP and AF becomes weaker.

FIGURE 2

Brief mechanism of CEP degradation mediated by different factors in the IDD cascade reaction. Natural degeneration, genetics, immunity, injury and smoking can affect CEP degeneration through multiple pathways and induce IDD.

FIGURE 3

CEP damage and Modic changes. On the one hand, CEP damage accompanied by Modic changes promotes inflammatory crosstalk between IVD and vertebral body. On the other hand, Modic changes cause substances in NP to directly contact with the body’s immune system and produce immune rejection, leading to damage to adjacent CEP structures.