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 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.e. 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.
Garnero
P
P
INSERM Unit 403, Hôpital E. Herriot, Pav F, 69437 Lyon cedex 03, France. garnero@cismsun.univ-lyon1.fr
Borel
O
O
Byrjalsen
I
I
Ferreras
M
M
Drake
F H
FH
McQueney
M S
MS
Foged
N T
NT
Delmas
P D
PD
Delaissé
J M
JM
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000737:chemistry; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D002417:Cattle; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000737:chemistry; D013379:Substrate Specificity
D010446:Peptide Fragments; D011994:Recombinant Proteins; D003094:Collagen; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K