Glycosaminoglycans Contribute To Skeletal Abnormalities In Patients With Lysosomal Storage Diseases

Their report can be found in the November 2009 issue of The American Journal of Pathology.

Mucopolysaccharidoses (MPS) are a group of diseases in which the dysfunction of a lysosomal enzyme results in decreased breakdown of GAGs, a type of carbohydrate, in various tissues. These GAGs then collect in cells, causing severe cellular damage that affects bone, skeletal structure, connective tissue, and organs.

In cells that break down bone, GAGs have been shown to inhibit the function of cathepsin K, an enzyme that breaks down collagen, which leads to insufficient space for new bone formation. As MPS patients have severe deficiencies in bone growth and development, Wilson et al hypothesized that cathepsin K inhibition may contribute to bone pathology in MPS patients. They found that both GAGs and cathepsin K were expressed in bone growth regions of a mouse model of MPS type I and that higher levels of cartilage accumulated in bone growth regions of MPS I mice than in their wild-type counterparts. In addition, cathepsin K-mediated collagen degradation was significantly reduced in bone-resorbing cells from MPS I mice.

Taken together, the data by Dr. Brömme and colleagues suggest that "the decrease in the collagenolytic activity of cathepsin K due to the expression of GAGs will greatly reduce osteoclast function and will thus likely contribute to the skeletal abnormalities observed in MPS I bone."