Disorders of the intervertebral disc (IVD) are the most common of musculoskeletal conditions. Environmental factors such as physical activity and mechanical loading may only explain a small subset of disc degeneration cases when compared to inherited genetic factors. Genetic analyses of human populations with disc disorders point toward substitution mutations in the chains of the type IX collagen molecule as being linked to a predisposition to IVD disorders.

Spinal structures of mice homozygous for an inactivation of the gene encoding the ai chain of type IX collagen were evaluated at multiple time points. A semiquantitative scheme for grading histological sections was utilized to assess morphological differences in the endplate and IVD. Microcomputed tomography was used to test for bony changes in the endplate and vertebral bodies. Finally, microdialysis was used to measure metabolite levels in an organ culture model. The primary motivation for this research was to test the hypothesis that the type IX collagen deletion leads to IVD degeneration and is associated with structural changes in adjacent bony elements, which may influence nutrient levels, cell metabolism and viability.

Early signs of degeneration were observed in the type IX collagen-deficient mice, primarily in the IVD region. The majority of genotype-related differences in bone structure were in the vertebral body cancellous bone. The type IX collagendeficient animals demonstrated a lower quality of cancellous bone structure, including reduced bone volume, fewer trabeculae, and increased trabecular separation. Finally, the organ culture and microdialysis study presented unique technical challenges and demonstrated no genotype-related differences in IVD metabolite levels.

This study demonstrated that the absence of type IX collagen, in the murine model, results in premature IVD degeneration and significant structural alterations in the adjacent cancellous bone of the vertebrae. Few changes were detected in the endplate region. The type IX collagen deletion mice may be a useful model of premature and spontaneous IVD degeneration, with the benefit of age-matched and littermate controls. The cellular and structural changes linked to this genetic mutation in a key matrix protein may provide additional insight into the treatment of IVD degeneration and low back pain.