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

Abstract

The cartilaginous endplates (CEP) are key components of the intervertebral disc (IVD) necessary for sustaining the nutrition of the disc while distributing mechanical loads and preventing the disc from bulging into the adjacent vertebral body. The size, shape, and composition of the CEP are essential in maintaining its function, and degeneration of the CEP is considered a contributor to early IVD degeneration. In addition, the CEP is implicated in Modic changes, which are often associated with low back pain. This review aims to tackle the current knowledge of the CEP regarding its structure, composition, permeability, and mechanical role in a healthy disc, how they change with degeneration, and how they connect to IVD degeneration and low back pain. Additionally, the authors suggest a standardized naming convention regarding the CEP and bony endplate and suggest avoiding the term vertebral endplate. Currently, there is limited data on the CEP itself as reported data is often a combination of CEP and bony endplate, or the CEP is considered as articular cartilage. However, it is clear the CEP is a unique tissue type that differs from articular cartilage, bony endplate, and other IVD tissues. Thus, future research should investigate the CEP separately to fully understand its role in healthy and degenerated IVDs. Further, most IVD regeneration therapies in development failed to address, or even considered the CEP, despite its key role in nutrition and mechanical stability within the IVD. Thus, the CEP should be considered and potentially targeted for future sustainable treatments.

Keywords: biologic therapies; biomechanics; degeneration; pre‐clinical models.

FIGURE 1

(A) Healthy CEP. In the healthy CEP, the collagen fibers of the AF continue into the CEP parallel to the bone (bottom). The collagen fibers of the NP penetrate at least partially into the CEP (top). The BEP–CEP junction is seen as a straight line with no gaps. CEP chondrocytes are rounded, and slightly elongated in the direction of the collagen fibers. The healthy CEP is avascular but has a base that contains a dense network of capillaries formed by terminal branches of metaphyseal and nutrient arteries. (B) Degenerative CEP. A degenerated CEP shows loss of thickness, fibrosis, calcification, and apoptotic cells. Fissures allow for blood vessels and nerve ingrowth as well as bacteria entering the NP (top). The adjacent BEP can show sclerosis and signs of MC (top). Avulsions of the CEP from the BEP can also occur (bottom). Integration between the CEP and the NP or AF can also become weaker. These degenerative changes can be identified histologically. Note that details regarding the other IVD tissues are not included in the image.

FIGURE 2

Healthy CEP diffusivity to different types of solutes based on their charge for small molecules and/or on their size and shape for large molecules. The molecules and diffusivities are based on Roberts et al. and Sampson et al.

FIGURE 3

Examples of CEP and BEP appearance in standard of care MRI from 47‐year‐old participants in the Northern Finland Birth Cohort 1966. (A.1–A.2) Characteristic appearance of healthy CEP and BEP on T1‐ and T2‐weighted MRI. (B.1) Schmorl's node as an example of a focal defect at the L3–L4 IVD caudal BEP (white arrow); (B.2) corner defects at the anterior edges of the L4–L5 IVD cranial and caudal BEP (white arrows) with accompanying type 2 MC (orange arrows); (B.3) erosive defects at the L4–L5 IVD cranial and caudal BEP (white arrows) with accompanying type 2 MC (orange arrows); (C.1–C.2) type 1 MC extending from the L3–L4 IVD cranial and caudal BEP (green arrows) with type 2 MC also visible in the L4 vertebral body (orange arrows); (C.3–C.4) type 2 MC extending from the L5–S1 IVD cranial and caudal BEP (orange arrows); (C.5–C.6) type 2 and type 3 MC (orange and blue arrows, respectively) extending from the L5–S1 IVD cranial and caudal BEP.

FIGURE 4

Hematoxylin and Eosin staining of human cartilaginous end plates (CEP) demonstrating key histological features of non‐degenerate and degenerate CEP. (A) Non‐degenerate CEP with BEP top left of image, CEP within region of the NP. (B) CEP within the region of NP demonstrating excellent maintenance of eosin staining. (C) CEP/AF enthesis within a non‐degenerate region, image shows BEP at bottom left and CEP within the middle connecting into AF. (D) CEP within region of AF tissue demonstrating change in matrix organization at bottom of image. (E) Abnormal CEP demonstrating clear disorganization and fibrosis. (F) Abnormal CEP showing fissures and disorganization of the CEP. (G) Abnormal CEP showing disorganization of the extracellular matrix. (H) Abnormal BEP/CEP enthesis with boney evulsion shown. Scale bars as indicated: 100 μm (A, B, D, E, G, and H), 200 μm (C and F).