Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

Abstract

The objective of this study was to assess the impact of a landmark annular lesion model on our understanding of the etiopathogenesis of IVD degeneration and to appraise current IVD repairative strategies. A number of studies have utilised the Osti sheep model since its development in 1990. The experimental questions posed at that time are covered in this review, as are significant recent advances in annular repair strategies. The ovine model has provided important spatial and temporal insights into the longitudinal development of annular lesions and how they impact on other discal and paradiscal components such as the NP, cartilaginous end plates, zygapophyseal joints and vertebral bone and blood vessels. Important recent advances have been made in biomatrix design for IVD repair and in the oriented and dynamic culture of annular fibrochondrocytes into planar, spatially relevant, annular type structures.

Topographical variation in the distributions of versican, aggrecan and perlecan in the foetal human spine reflects their diverse functional roles in spinal development

“…Perlecan (HSPG2), a HS-substituted matrix proteoglycan, is also a prominent component of the primordial cartilaginous rudiments in the developing spine and a component of small blood vessels in the looser connective tissues surrounding these structures (Arikawa-Hirasawa et al 1999;Gustafsson et al 2003;Melrose et al 2002Melrose et al , 2003Melrose et al , 2008a. A greater understanding of how these spinal components are assembled may provide valuable clues as to how to best approach their biological repair in mature tissues (Kalson et al 2008;Melrose et al 2008b;Richardson et al 2007;Zhang et al 2008).…”

The Role of Cell Clusters in Intervertebral Disc Degeneration and its Relevance behind Repair

“…Presumably, cluster formation reflects the influence of the immediate pericellular matrix on the cells through continued accumulation of cell products, as the np region of the IVDs occurs in a relatively confined environment [25]. Cluster formation in the nucleus pulposus and inner annulus regions has been linked to gross structural changes that occur mainly during aging or injury [37].…”

Mesenchymal stem cell tracking in the intervertebral disc

“…With the loss of the water binding PGs from the disc, its functional capacity as a hydroelastic cushion is diminished, leading to additional mechanical stresses acting on the fibrocartilagenous AF. With time, these events can result in the presence of concentric and radiating tears in the lamellae of the AF that may eventually extend into the NP [7,8,[11][12][13] . In addition, there is emerging evidence that damage to the cartilaginous endplate plays a role in the pathophysiology of degenerative disc disease, up-regulating matrix degrading enzymes and inflammatory cytokines in the NP [14] .…”

“…In addition, there is emerging evidence that damage to the cartilaginous endplate plays a role in the pathophysiology of degenerative disc disease, up-regulating matrix degrading enzymes and inflammatory cytokines in the NP [14] . Structural deficiencies in the NP are considered to provoke neovascularisation and growth of nerve fibers, normally confined to the periphery of the AF, to the deeper regions of the disc [13,15] . The establishment of these extended nerve fibers has been cited as a major cause of chronic lower back pain in degenerate discs [15][16][17] .…”