Proteoglycans (PGs) are macromolecules present on the cell surface and in the extracellular matrix that confer specific mechanical, biochemical, and physical properties to tissues.
Sulfate groups present on
glycosaminoglycans, linear
polysaccharide chains attached to PG core
proteins, are fundamental for correct PG functions. Indeed, through the negative charge of
sulfate groups, PGs interact with extracellular matrix molecules and bind
growth factors regulating tissue structure and cell behavior. The maintenance of correct
sulfate metabolism is important in tissue development and function, particularly in cartilage where PGs are fundamental and abundant components of the extracellular matrix. In chondrocytes, the main
sulfate source is the extracellular space, then
sulfate is taken up and activated in the cytosol to the universal
sulfate donor to be used in
sulfotransferase reactions. Alteration in each step of
sulfate metabolism can affect macromolecular sulfation, leading to the onset of diseases that affect mainly cartilage and bone. This review presents a panoramic view of skeletal dysplasias caused by mutations in genes encoding for transporters or
enzymes involved in macromolecular sulfation. Future research in this field will contribute to the understanding of the disease pathogenesis, allowing the development of targeted
therapies aimed at alleviating, preventing, or modifying the
disease progression.