Variation in chondroadherin abundance and fragmentation in the human scoliotic disc.

Variation in abundance and structure of chondroadherin (CHAD) were studied in the extracellular matrix (ECM) of scoliotic and normal human discs. To determine whether CHAD abundance and fragmentation vary between different sides of the scoliotic disc and between scoliotic and normal discs. Scoliosis involves curvature of the spine including wedging of the intervertebral discs (IVDs), resulting in altered mechanical loading, which can influence cell metabolism and matrix structure in the IVD. A protein such as CHAD that can influence both cell metabolism and ECM organization could influence disc pathology in scoliosis. IVDs were obtained from patients with scoliosis and from normal individuals. A proteomic analysis was performed to identify molecules that exhibit side-specific variations in abundance. In addition, changes in the abundance and fragmentation of CHAD and other members of the leucine-rich repeat protein family were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Aggrecan fragmentation was used as an indicator of proteinase action. The relative amount of CHAD was consistently lower on the concave side of the discs in all patients studied. In addition, proteolytic degradation of CHAD occurred in some patients with scoliosis, but not in normal IVDs. The presence of aggrecan fragments provided evidence for both aggrecanase and metalloproteinase activity in the scoliotic discs although no side-specific difference was found. Other members of the leucine-rich repeat family of proteins did not show evidence of the same consistent variation in abundance between the 2 sides and did not show signs of degradation. As CHAD can interact with both the ECM and the cells, it can provide a mechanism for regulating cell metabolism and ECM structure, and so play a role in promoting matrix homeostasis. Thus, changes in CHAD abundance or structure could be associated with the pathologic changes occurring in the scoliotic IVD.