Cartilage Oligomeric Matrix Protein in Canine Spinal Cord Appears in the Cerebrospinal Fluid Associated With Intervertebral Disc Herniation

Abstract

Cerebrospinal fluid (CSF) from dogs with intervertebral disc herniation (IVDH) were analyzed using a specific antibody against cartilage oligomeric matrix protein (COMP). Immunolocalization and genetic expression of COMP were also examined in the spinal cords of mouse, rat, and dog. To investigate the hypothesis that COMP is present in CSF of dogs with IVDH, and the clinical relevance of COMP expression in CSF as a potential biomarker of spinal cord injury. In dog IVDH, diagnostic imaging is useful for determining the spinal cord compression, but less useful for assessment of traumatic degeneration. Aggrecan, a well-known component of cartilage matrix, is increased in CSF from cases of neural damage and inflammation of the spinal cord. CSF from the cisterna magna (C-CSF) and the lumbar spine (L-CSF) of 19 dogs with IVDH and 5 normal dogs were analyzed using inhibition enzyme-linked immunosorbent assay (ELISA) and immunoblotting with an antibody cross-reactive with dog COMP. Samples of normal spinal cord from mouse, rat, and dog were also prepared for immunohistochemistry and in situ hybridization. ELISA values were significantly higher for L-CSF than for C-CSF in dogs with IVDH, whereas there was no significant difference between them in normal dogs. Immunoblots of L-CSF samples revealed positive bands of approximately 500 kDa in 6 cases of IVDH (positive cases), but no signal in negative cases. ELISA values were significantly higher in the positive cases than in the negative cases. Both COMP protein and mRNA were present at high levels in the gray matter of the spinal cord in all species. In dog IVDH, release of COMP from the spinal cord in association with injury may lead to COMP accumulation in L-CSF posterior to the site of disc extrusion, and therefore might be a predictive marker of spinal cord injury.