title: Aggrecan heterogeneity in articular cartilage from patients with osteoarthritis.
abstract: BACKGROUND
  Aggrecan degradation is the hallmark of cartilage degeneration in osteoarthritis (OA), though it is unclear whether a common proteolytic process occurs in all individuals.
  
  
  METHODS
  Aggrecan degradation in articular cartilage from the knees of 33 individuals with OA, who were undergoing joint replacement surgery, was studied by immunoblotting of tissue extracts.
  
  
  RESULTS
  Matrix metalloproteinases (MMPs) and aggrecanases are the major proteases involved in aggrecan degradation within the cartilage, though the proportion of aggrecan cleavage attributable to MMPs or aggrecanases was variable between individuals. However, aggrecanases were more associated with the increase in aggrecan loss associated with OA than MMPs. While the extent of aggrecan cleavage was highly variable between individuals, it was greatest in areas of cartilage adjacent to sites of cartilage erosion compared to sites more remote within the same joint. Analysis of link protein shows that in some individuals additional proteolytic mechanisms must also be involved to some extent.
  
  
  CONCLUSIONS
  The present studies indicate that there is no one protease, or a fixed combination of proteases, responsible for cartilage degradation in OA. Thus, rather than targeting the individual proteases for OA therapy, directing research to techniques that control global protease generation may be more productive.
authors.affiliation: Research Unit, Shriners Hospital for Children, 1003, boul. Décarie, Montreal, Quebec, H4A 0A9, Canada. jmort@shriners.mcgill.ca.|Department of Surgery, McGill University, Montreal, Quebec, Canada. jmort@shriners.mcgill.ca.
authors.forename: John S
authors.initials: JS
authors.lastname: Mort
authors.affiliation: Research Unit, Shriners Hospital for Children, 1003, boul. Décarie, Montreal, Quebec, H4A 0A9, Canada. yqgeng@shriners.mcgill.ca.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Department of Surgery, McGill University, Montreal, Quebec, Canada. wfisher@sympatico.ca.|Division of Orthopaedics, McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada. wfisher@sympatico.ca.
authors.forename: William D
authors.initials: WD
authors.lastname: Fisher
authors.affiliation: Research Unit, Shriners Hospital for Children, 1003, boul. Décarie, Montreal, Quebec, H4A 0A9, Canada. proughley@shriners.mcgill.ca.|Department of Surgery, McGill University, Montreal, Quebec, Canada. proughley@shriners.mcgill.ca.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Roughley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans / Q000032:analysis* / Q000378:metabolism; D002358:Cartilage, Articular / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000175:diagnosis* / Q000378:metabolism
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans