Early‐onset degeneration of the intervertebral disc and vertebral end plate in mice deficient in type IX collagen

Abstract

Type IX collagen is an important component of the intervertebral disc extracellular matrix. Mutations in type IX collagen are associated with premature disc degeneration in mice and a predisposition to disc disorders in humans. The aim of this study was to assess the prevalence and timeline of intervertebral disc degeneration in mice homozygous for an inactivated Col9a1 gene. Intact spine segments were harvested from wild-type (WT) and type IX collagen-knockout (Col9a1(-/-)) mice at 3, 6, and 12 months of age. Sagittal spine sections were evaluated for evidence of histologic changes, by 2 blinded graders, using a semiquantitative grading method. There was evidence of more degeneration of the disc and end plate in the spines of Col9a1(-/-) mice compared with those of WT controls, at most time points. These findings were significant for the disc region at 3 and 6 months (P<0.01) and at 12 months (P<0.10) and for the end plate region only at 6 months (P<0.10). Degenerative changes in the disc consisted of cellular changes and mucous degeneration. Degeneration in the end plates was associated with more cell proliferation, cartilage disorganization, and new bone formation. A deletion mutation for type IX collagen is associated with connective tissue changes characteristic of musculoskeletal degeneration in bony and cartilaginous tissue regions. Some of the observed changes were similar to cartilage changes in osteoarthritis, while others were more similar to disc degenerative changes in humans. The finding of premature onset of intervertebral disc degeneration in this mouse model may be useful in studies of the pathology and treatment of human disc degeneration.