# The Impact of the Ovine Annular Lesion Model on IVD Pathobiology and Utility of the Ovine Spinal Model in Patho‐Anatomical Studies: A Historical Perspective

## TL;DR

This paper reviews the ovine annular lesion model's role in understanding intervertebral disc degeneration and its relevance to human spinal conditions.

## Contribution

Highlights the ovine model's unique similarity to human IVD degeneration and its utility for evaluating repair strategies.

## Key findings

- The ovine model shows similar degenerative features to human IVD, making it a valuable translational tool.
- Degeneration in the ovine IVD leads to biomechanical impairment and low back pain, mirroring human conditions.
- The model allows for interdisciplinary studies and evaluation of regenerative therapies for IVD repair.

## Abstract

This review documents the impact of the Osti ovine annular lesion model of intervertebral disc (IVD) degeneration on the elucidation of degenerative changes in the ovine IVD also seen in human IVD degeneration (IVDD). The degenerative pathology knowledge base generated by the ovine model over the last 35 years has provided invaluable insights into degenerative events occurring in the human IVD. Changes in para‐discal structures as a consequence of IVDD, in vertebral bone adjacent to the lesion site, cartilaginous endplates and spinal motion segment facet joints, and in the longitudinal ligaments and paraspinal muscles also affect spinal stability and flexibility. All of these spinal structures are richly innervated, and disturbance of their normal architecture due to IVDD also contributes to the generation of low back pain. Like human IVDD, when the ovine IVD is mechanically destabilized by the introduction of a controlled annular lesion, release of proteases is elevated, degradation of structural ECM components occurs, leading to IVDD and biomechanical impairment. When space‐filling aggrecan is degraded in the IVD, a drop in internal hydrostatic pressure occurs, and the IVD becomes susceptible to an ingrowth of blood vessels and mechanosensitive nociceptors resulting in enhanced generation of low back pain by the biomechanically incompetent IVD. The ovine model is thus very useful to evaluate compounds or procedures that slow IVDD and, in some cases, promote regenerative processes. The large size of the ovine IVD allows the use of inter‐disciplinary longitudinal approaches in the analysis of progressive changes in the degenerate IVD of relevance to the human IVD.

The ovine annular lesion model of IVDD displays similar pathological features to those displayed by the degenerate human IVD, making it an appropriate model for the evaluation of IVD reparative procedures. Furthermore, the resident ovine IVD cell populations are similar to those seen in the human IVD, with a disappearance of notochordal cells occurring in adolescence. This is not the case in many other popular animal (murine, rat, porcine, lapine, and non‐chondrodystrophic canine) models of IVDD. The persistence of notochordal cells into adulthood in these breeds questions how translatable findings generated in these models are to the human IVD. The ovine model is thus relevant to the development of strategies exploring novel strategies in IVD repair and the recovery of normal IVD structure and function. Mesenchymal stem cells have impressive IVD repair and recovery of structure and function properties, showing promise in the treatment of the degenerate human IVD.

The ovine annular rim‐lesion model of intervertebral disc degeneration of Osti and colleagues (1990) has evolved into a sophisticated mechanical destabilization large animal model of intervertebral disc degeneration over its 35 year history offering diverse musculoskeletal multi‐disciplinary investigations into the multifunctional complexity of this condition relevant to the human condition.