Heparan Sulfate Proteoglycans: Key Players in Cartilage Biology

The extracellular matrix (ECM) plays a fundamental role in skeletal patterning and formation of the vertebrate skeleton. This review focuses on the fundamental roles associated with heparan sulfate (HS) proteoglycans in the ECM during cartilage development, which include regulation of gene expression, presentation of growth factors, establishment of morphogen gradients, and modulation of blood homeostasis. The importance of enzymes involved in biosynthesis and assembly of heparan sulfate is also discussed. Finally, the current evidence for functions of individual HS proteoglycans and biosynthetic enzymes based upon human genetic mutation associations with disease and genetic manipulation in transgenic mice is presented. These findings highlight the important role played by HS proteoglycans, such as perlecan, in cartilage development and skeletal growth.