The Collagenolytic Activity of Cathepsin K Is Unique among Mammalian Proteinases

TLDR

Type I collagen makes up 90 % of bone’s organic matrix, and its degradation during bone resorption is a key but poorly understood process in which cathepsin K is suspected to play a central role. Cathepsin K alone completely dissolves insoluble adult human cortical bone collagen, cleaving both non‑helical and helical regions—a unique collagenolytic capability among mammalian proteinases that likely underlies its pivotal role in bone resorption.

Abstract

Type I collagen fibers account for 90% of the organic matrix of bone. The degradation of this collagen is a major event during bone resorption, but its mechanism is unknown. A series of data obtained in biological models strongly suggests that the recently discovered cysteine proteinase cathepsin K plays a key role in bone resorption. Little is known, however, about the actual action of cathepsin K on type I collagen. Here, we show that the activity of cathepsin K alone is sufficient to 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>i.e.</i> the typical activity 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 proteinases and is reminiscent of bacterial collagenases. It is likely to be responsible for the key role of cathepsin K in bone resorption.