Cleavage of type II collagen by cathepsin K in human osteoarthritic cartilage.
Cathepsin K is a cysteine protease of the papain family that cleaves triple-helical type II collagen, the major structural component of the extracellular matrix of articular cartilage. In osteoarthritis (OA), the anabolic/catabolic balance of articular cartilage is disrupted with the excessive cleavage of collagen II by collagenases or matrix metalloproteinases. A polyclonal antibody against a C-terminal neoepitope (C2K) generated in triple-helical type II collagen by the proteolytic action of cathepsin K was prepared and used to develop an enzyme-linked immunosorbent assay to study the generation of this epitope and the effects of its presence in normal adult and osteoarthritic femoral condylar articular cartilage. The generation of the C2K epitope in explant culture and the effect of a specific cathepsin K inhibitor were studied. The neoepitope, which is not generated by the collagenase matrix metalloproteinase-13, increased with age in articular cartilage and was significantly elevated in osteoarthritic cartilage compared with adult nonarthritic cartilage. Moreover, in explants from three of eight OA patients, the generation of the neoepitope in culture was significantly reduced by a specific, nontoxic inhibitor of cathepsin K. These data suggest that cathepsin K is involved in the cleavage of type II collagen in human articular cartilage in certain OA patients and that it may play a role in both OA pathophysiology and the aging process.
Joint Diseases Laboratory, Shriners Hospitals for Children, 1529 Cedar Ave., Montreal, Quebec, H3G1A6, Canada. vdejica@shriners.mcgill.ca
Valeria M
VM
Dejica
John S
JS
Mort
Sheila
S
Laverty
M David
MD
Percival
John
J
Antoniou
David J
DJ
Zukor
A Robin
AR
Poole
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D001483:Base Sequence; D001713:Biphenyl Compounds / Q000494:pharmacology; D002358:Cartilage, Articular / Q000378:metabolism* / Q000503:physiopathology; D056657:Cathepsin K; D002403:Cathepsins / Q000187:drug effects / Q000378:metabolism*; D024043:Collagen Type II / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000503:physiopathology; D010455:Peptides / Q000187:drug effects / Q000378:metabolism
D001713:Biphenyl Compounds; D024043:Collagen Type II; D004791:Enzyme Inhibitors; C527129:L-873724; D010455:Peptides; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K