title: Relationship between synovial fluid levels of glycosaminoglycans, hydroxyproline and general MMP activity and the presence and severity of articular cartilage change on the proximal articular surface of P1.
abstract: BACKGROUND
  Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting horses and leads to degeneration of articular cartilage. Diagnosis is based on clinical signs in combination with radiography, which is relatively insensitive and provides only an indication of accumulated damage. Alternative methods, such as molecular markers, are therefore needed that can quantitatively, reliably and sensitively detect osteoarthritic changes in the joints at an early stage of the disease. If such markers are to be used reliably, it is important to know the relationship between marker concentration and cartilage composition.
  
  
  OBJECTIVE
  To study the relationship between cartilage composition, synovial fluid levels of glycosaminoglycans (GAGs), hydroxyproline (Hyp) and general matrix metalloproteinase (MMP) activity, and the presence and severity of articular cartilage damage on the articular surface of P1.
  
  
  METHODS
  Synovial fluid (SF) was collected from the metacarpophalangeal joints of 60 mature horses, and levels of GAGs, Hyp and general MMP activity were determined. Further, GAG and denatured collagen content of the articular cartilage were determined at the dorsal articular margin of P1 (site 1) and central cavity (site 2). The presence and severity of cartilage change was quantified using the cartilage degeneration index (CDI), measured at the same 2 sites. Correlations between SF parameters, cartilage composition and degree of cartilage degeneration were sought using correlation analysis.
  
  
  RESULTS
  There was no correlation between GAG or Hyp content of SF and the amount of GAGs or denatured collagen, respectively, in cartilage. In joints with moderate to severe cartilage damage, the GAG content of site 1 was significantly lower than in joints with no to minimal cartilage change (P = 0.005) and there was a negative correlation between the amount of denatured collagen and GAG content at site 1 in all joints (r = -039, P = 0.002). Further, in joints with moderate to severe cartilage damage, there was a significant positive correlation between MMP activity in SF and Hyp levels in SF (r = 0.72, P < 0.001) and CDI at sites 1 (r = 0.46, P = 0.03) and 2 (r = 0.43, P = 0.04).
  
  
  CONCLUSIONS
  General MMP activity in joints with moderate to severe cartilage damage is related to the severity of those cartilage changes and to Hyp levels in SF. Glycosaminoglycan levels in SF are not directly related to MMP activity, GAG content of articular cartilage or severity of cartilage change.
  
  
  CONCLUSIONS
  Glycosaminoglycan levels in SF are not helpful for the early detection of cartilage lesions. In damaged joints, Hyp levels may give an indication of the severity of cartilage change as they are strongly related to MMP activity, but do not qualify as markers for the presence or absence of cartilage lesions.
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van den Boom
authors.forename: M R
authors.initials: MR
authors.lastname: van der Harst
authors.forename: H
authors.initials: H
authors.lastname: Brommer
authors.forename: P A J
authors.initials: PA
authors.lastname: Brama
authors.forename: A
authors.initials: A
authors.lastname: Barneveld
authors.forename: P R
authors.initials: PR
authors.lastname: van Weeren
authors.forename: J
authors.initials: J
authors.lastname: DeGroot
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002358:Cartilage, Articular / Q000473:pathology*; D006025:Glycosaminoglycans / Q000032:analysis* / Q000378:metabolism; D006734:Horse Diseases / Q000175:diagnosis / Q000473:pathology; D006736:Horses; D006909:Hydroxyproline / Q000032:analysis* / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010003:Osteoarthritis / Q000175:diagnosis / Q000473:pathology / Q000662:veterinary; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000737:chemistry* / Q000201:enzymology
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; D020782:Matrix Metalloproteinases; D006909:Hydroxyproline