title: Chondrocyte-mediated collagenolysis correlates with cartilage destruction grades in osteoarthritis.
abstract: OBJECTIVE
  Osteoarthritis (OA) is associated with destruction of type II collagen-rich hyaline articular cartilage. We hypothesized that classical interstitial collagenases cleave collagen type II, leading to the increased expression of the 3/4 native type II collagen fragment (COL2-3/4C) and the corresponding denatured type II collagen fragment (COL2-3/4M), which could correlate with different cartilage destruction grades. In addition, we assessed whether these fragments could be measured in joint fluid and serve as diagnostic markers.
  
  
  METHODS
  Cartilage specimens were obtained from the femoral heads of hip joints from total hip replacement operations. Articular gliding surfaces of the cartilage were categorized into normal (G0), fibrillated (G1), superficiallyfissured (G2) and deeplyfissured (fissures that reach to the subchondral bone) (G3). A histological scoring of the cartilage was also used. COL2-3/4C and COL2-3/4M were detected by immunohistochemical staining. Dot blotting was used to detect these fragments in joint fluid.
  
  
  RESULTS
  COL2-3/4C and COL2-3/4M were found in the perichondrocyte matrix around lacunae. Such COL2-3/4C (p < 0.05) and COL2-3/4M (p < 0.05) immunoreactivity was significantly increased in G3 and G2 compared to GO and G1. A positive correlation (n = 35, Spearman rank correlation) was observed between the histological score and the percentage of COL2-3/4C positive lacunae (r = 0.43, p = 0.01) and COL2- 3/4M positive lacunae (r = 0.53, p = 0.001). All 7/7 joint fluid samples contained COL2-3/4C in dot blots whereas only 4/7 contained COL2-3/4M.
  
  
  CONCLUSIONS
  Collagenase-cleaved collagen--both native and denatured--increases as the severity of OA increases, assessed using a macroscopic clinical and microscopic histological grading system. Collagen degradation was always most apparent around chondrocytes. Furthermore, the native COL2-3/4C fragment has potential as a joint fluid marker for OA.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Finland. yrjo.konttinen@helsinki.fi
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: P
authors.initials: P
authors.lastname: Ruuttilal
authors.forename: M
authors.initials: M
authors.lastname: Hukkanen
authors.forename: S
authors.initials: S
authors.lastname: Santavirta
mesh_terms: D000368:Aged; D015415:Biomarkers; D002357:Cartilage Diseases / Q000378:metabolism / Q000503:physiopathology*; D002358:Cartilage, Articular / Q000503:physiopathology; D019902:Chondrocytes / Q000502:physiology; D024043:Collagen Type II / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D006801:Humans; D015207:Osteoarthritis, Hip / Q000378:metabolism / Q000503:physiopathology*; D013582:Synovial Fluid / Q000737:chemistry / Q000502:physiology
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D017364:Collagenases