title: Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic processing of type II collagen.
abstract: OBJECTIVE
  The aim of the present study was to investigate collagen metabolism after anabolic and catabolic stimulation of chondrocytes ex vivo.
  
  
  METHODS
  Metabolic activities in ex vivo bovine cartilage explants were stimulated with insulin-like growth factor I (IGF-I) or a combination of tumor necrosis factor alpha (TNFalpha) and oncostatin M (OSM). Supernatants were assessed for changes in biochemical markers, N-terminal propeptide of type II (PIINP) collagen and fragments of C-telopeptide of type II collagen (CTX-II). Matrix metalloproteinases (MMP) were added to metabolic inactivated cartilage and evaluated by the two biochemical markers for formation or degradation, respectively. Finally, urinary CTX-II and PIINP were evaluated for assessment of type II collagen turnover in patients with rheumatoid arthritis (RA).
  
  
  RESULTS
  In the bovine articular cartilage explants, IGF-I induced an increase in PIINP level up to 4.8+/-1.1[ng/ml]/mg cartilage whereas CTX-II remained below 0.1+/-0.1[ng/ml]/mg cartilage. In the catabolic stimulated explants both PIINP and CTX-II were released to the supernatant, reaching concentrations of 9.0+/-1.4 and 9.1+/-2.2[ng/ml]/mg cartilage, respectively. RA patients had significantly lower serum concentrations of PIINP (3.4+/-3.7 ng/ml) compared with those healthy individuals (18.7+/-12.41 ng/ml, P<0.001). In contrast, RA patients had significantly higher urinary CTX-II (0.8+/-0.8 mg/mmol) compared to the healthy controls (0.1+/-0.08 mg/mmol, P=0.004).
  
  
  CONCLUSIONS
  This study is the first to demonstrate that precursors and degradation products of type II collagen released into the supernatant can effectively reflect the anabolic and catabolic activities of stimulated cartilage explants.
authors.affiliation: Nordic Bioscience Diagnostics A/S, Herlev, Denmark. ako@nordicbioscience.com
authors.forename: A K
authors.initials: AK
authors.lastname: Olsen
authors.forename: B C
authors.initials: BC
authors.lastname: Sondergaard
authors.forename: I
authors.initials: I
authors.lastname: Byrjalsen
authors.forename: L B
authors.initials: LB
authors.lastname: Tanko
authors.forename: C
authors.initials: C
authors.lastname: Christiansen
authors.forename: A
authors.initials: A
authors.lastname: Müller
authors.forename: G E
authors.initials: GE
authors.lastname: Hein
authors.forename: M A
authors.initials: MA
authors.lastname: Karsdal
authors.forename: P
authors.initials: P
authors.lastname: Qvist
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015415:Biomarkers; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D019902:Chondrocytes / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I; D010455:Peptides / Q000378:metabolism*; D011347:Procollagen / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D010455:Peptides; D011347:Procollagen; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I