The molecular basis of intervertebral disk degeneration

The human intervertebral disk (IVD) consists of two major regions: an outer ring of annulus fibrosis (AF) and an inner nucleus pulposus (NP) with a transitional zone that merges these two regions together (Fig. 1A). The disk is an avascular structure composed of an extracellular matrix embedded with chondrocyte-like and fibroblast-like cells. The AF is densely packed with rings of highly organized collagen type I fibril sheets. These sheets known as lamellae are perpendicular in direction to one another; fibrocytes are embedded among them (Fig. 113). Fibrocytes are dominant in the outer regions of the AF and the appearance of chondrocytes at the inner portion of the AF and within the NP. Collagen type I molecules confer the tensile strength of the disk similar to tendons, with a dry weight of 70% collagen within the AF and 20% within the central NP. The NP is a gelatinous structure in which water molecules are retained in the matrix by proteoglycans, and collagen type 11 molecules among which chondrocyte-like cells are suspended [1,2]. Fibrocyte-like and chondrocyte-like cells produce and maintain the matrix in which they are embedded. They are the major cell types in the disk and have good viability under such avascular conditions. There is a gradient of collagen types I and 11 across the disk, where type I collagen predominantly reside in the AF and slowly decrease in concentration toward the inner annulus. The collagen type 11 progressively increase in density as they proceed into the NP, occupying 85% of it. Types VI and XI collagen are also present. Superior and inferior to the intervertebral disk, they comprise the vertebral end plates, consisting of a thin layer of cortical bone covered by hyaline cartilage synthesized by chondrocytic cells [1].