title: Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage.
abstract: BACKGROUND
  The intra-helical cleavage of type II collagen by proteases, including collagenases and cathepsin K, is increased with aging and osteoarthritis (OA) in cartilage as determined by immunochemical assays. The distinct sites of collagen cleavage generated by collagenases and cathepsin K in healthy and OA human femoral condylar cartilages were identified and compared.
  
  
  METHODS
  Fixed frozen cartilage sections were examined immunohistochemically, using antibodies that react with the collagenase-generated cleavage neoepitopes, C2C and C1,2C, and the primary cleavage neoepitope (C2K) generated in type II collagen by the action of cathepsin K and possibly by other proteases, but not by any collagenases studied to date.
  
  
  RESULTS
  In most cases, the staining patterns for collagen cleavage were similar for all three epitopes: weak to moderate mainly pericellular staining in non-OA cartilage from younger individuals and stronger, more widespread staining in aging and OA cartilages that often extended from the superficial to the mid/deep zone of the tissue. In very degenerate OA specimens, with significant disruption of the articular surface, staining was distributed throughout most of the cartilage matrix.
  
  
  CONCLUSIONS
  Cleavage of collagen by proteases usually arises pericellularly around chondrocytes at and near the articular surface, subsequently becoming more intense and extending progressively deeper into the cartilage with aging and OA. The close correspondence between the distributions of these products suggests that both collagenases and cathepsin K, and other proteases that may generate this distinct cathepsin K cleavage site, are usually active in the same sites in the degradation of type II collagen.
authors.affiliation: Genetics Unit, Shriners Hospitals for Children, 1529 Cedar Avenue, Montreal, QC H3G 1A6, Canada.
authors.forename: Valeria M
authors.initials: VM
authors.lastname: Dejica
authors.forename: John S
authors.initials: JS
authors.lastname: Mort
authors.forename: Sheila
authors.initials: S
authors.lastname: Laverty
authors.forename: John
authors.initials: J
authors.lastname: Antoniou
authors.forename: David J
authors.initials: DJ
authors.lastname: Zukor
authors.forename: Michael
authors.initials: M
authors.lastname: Tanzer
authors.forename: A Robin
authors.initials: AR
authors.lastname: Poole
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D002102:Cadaver; D002358:Cartilage, Articular / Q000378:metabolism*; D056657:Cathepsin K / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D024043:Collagen Type II; D056657:Cathepsin K; D017364:Collagenases