THE COLLAGENOLYTIC ACTIVITY OF CATHEPSIN-K IS UNIQUE AMONG MAMMALIAN PROTEINASES

Type I collagen fibers account for 90% of the organic matrix of bone. The degradation of this collagen is a major event during bone resorpti on, but its mechanism is unknown. A series of data obtained in biologi cal models strongly suggests that the recently discovered cysteine pro teinase cathepsin K plays a key role in bone resorption, Little is kno wn, however, about the actual action of cathepsin K on type I collagen . Here, we show that the activity of cathepsin K alone is sufficient t o dissolve completely insoluble collagen of adult human cortical bone, We found that the collagenolytic activity of cathepsin K is directed both outside the helical region of the molecule, i.e, the typical acti vity of cysteine proteinases, and at various sites inside the helical region, hitherto believed to resist all mammalian proteinases but the collagenases of the matrix metalloproteinase family and the neutrophil elastase, This property of cathepsin K is unique among mammalian prot einases and is reminiscent of bacterial collagenases, It is likely to be responsible for the key role of cathepsin K in bone resorption.