Aggrecan, the major proteoglycan of cartilage that provides its mechanical properties of
compressibility and elasticity, is one of the first matrix components to undergo measurable
loss in arthritic diseases. Two major sites of proteolytic cleavage have been identified within
the interglobular domain (IGD) of the aggrecan core protein, one between amino acids Asn
341-Phe 342 which is cleaved by matrix metalloproteinases and the other between Glu 373-
Ala 374 that is attributed to aggrecanase. Although several potential aggrecanase-sensitive …