title: Elevation of a collagenase generated type II collagen neoepitope and proteoglycan epitopes in synovial fluid following induction of joint instability in the dog.
abstract: CONCLUSIONS
  Measurement of markers of cartilage pathology in synovial fluid may provide clinical rheumatologists and osteoarthritis (OA) researchers important information for early diagnosis of OA as well as a method for monitoring disease progression and response to treatment. This study demonstrates the value of this approach in an established model of OA (cranial cruciate ligament rupture) at a point distant enough from the original surgical manipulation so as to have little to no effect on the marker concentrations.
  
  
  OBJECTIVE
  The objective of this study was to determine whether measurement of markers of cartilage collagen cleavage and proteoglycan turnover in synovial fluid from a canine model could be used to detect cartilage changes following the onset of joint instability during the development of OA.
  
  
  METHODS
  A model of joint instability that develops OA was created in 18 mature dogs using monopolar radiofrequency energy (MRFE). MRFE was arthroscopically applied to one cranial cruciate ligament (CCL) while the contralateral CCL was sham treated. The treated CCLs ruptured approximately 8 weeks (55 +/- 1.6 days) after MRFE treatment. Synovial fluid was collected at time zero prior to MRFE treatment, 4 weeks after MRFE treatment, and at 4, 8, and 16 weeks after CCL rupture. Synovial fluid concentrations of the neoepitope COL2-3/4C long (type II collagen cleavage by collagenase) and epitopes 3B3(-) (proteoglycan aggrecan sulfation) and 846 (associated with aggrecan synthesis) were analyzed.
  
  
  RESULTS
  Compared to sham treated joints, the synovial fluid concentrations of COL2-3/4C long and 3B3(-) were significantly increased 2.2 fold and 2.9 fold, respectively, in joints with MRFE treated CCLs following CCL rupture. Concentrations of the 846 epitope in synovial fluid showed a trend toward an increase, which was not significant, after CCL rupture.
  
  
  CONCLUSIONS
  Concentrations of the collagenase-cleaved type II collagen neoepitope and 3B3(-) epitope in synovial fluid were significantly increased by 4 weeks and remained elevated for at least 16 weeks after CCL rupture. This suggests that in dogs the COL2-3/4C long neoepitope and 3B3(-) epitope are sensitive markers for changes in joint cartilage turnover in joints that are developing OA.
authors.affiliation: Comparative Orthopaedic Research Laboratory, Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Chu
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Ionescu
authors.forename: R C
authors.initials: RC
authors.lastname: Billinghurst
authors.forename: K A
authors.initials: KA
authors.lastname: Johnson
authors.forename: A R
authors.initials: AR
authors.lastname: Poole
authors.forename: M D
authors.initials: MD
authors.lastname: Markel
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D024043:Collagen Type II / Q000032:analysis*; D017364:Collagenases / Q000378:metabolism*; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis; D006614:Hindlimb / Q000378:metabolism; D007593:Joint Instability / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D008023:Ligaments, Articular / Q000293:injuries / Q000378:metabolism; D010003:Osteoarthritis / Q000175:diagnosis* / Q000378:metabolism; D011509:Proteoglycans / Q000032:analysis*; D011846:Radio Waves; D012421:Rupture / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D000939:Epitopes; D011509:Proteoglycans; D017364:Collagenases