The potential and limitations of cartilage-specific (V + C)^- fibronectin and cartilage oligomeric matrix protein as osteoarthritis biomarkers in canine synovial fluid

Objective: To determine if levels of the cartilage-specific (V + C)^- fibronectin isoform in the synovial fluid is associated with cartilage change during osteoarthritis. Design: Synovial fluid was collected from 26 healthy dogs presenting to the Orthopedic Surgery Clinic with unilateral cranial cruciate rupture, 22 control dogs, and 13 dogs from a colony maintained for the study of canine hip dysplasia. Total fibronectin, (V + C)^- fibronectin, and cartilage oligomeric matrix protein (COMP) were quantitated by ELISA assays. Statistical analysis used Wilcoxon's signed-rank and rank-sum tests and Spearman's rank correlation. Results: The concentration of total fibronectin was increased in affected (P < 0.0001) and contralateral (P = 0.0005) knees of the clinic population (compared to unaffected knees in colony controls). Both (V + C)^- fibronectin and COMP concentrations were elevated in the contralateral knees in clinical patients relative to unaffected knees in the colony controls (P = 0.03 and P = 0.04, respectively), and relative to the affected knees (P = 0.003); however, corrections for joint effusions suggest elevated totals in the affected knees. (V + C)^- fibronectin and COMP concentrations were correlated (r_sp 74; P < 0.0001) in 30 unaffected knees of patients and colony controls. Total fibronectin was correlated negatively with months since the initial injury (r_sp = -0.44; P = 0.03) in the affected joints. The intraoperative lesion severity score did not correlate with total fibronectin or (V + C)^- fibronectin (P ≥ 0.35). Conclusions: Concentration of total fibronectin in synovial fluid might be a useful biomarker for cross-sectional studies in osteoarthritis, but only (V + C)^- fibronectin provides information specifically about cartilage damage. Elevated concentrations of (V + C)^- fibronectin and COMP seen in the contralateral knees of patients with cranial cruciate rupture might indicate cartilage changes early in the disease process (pre-clinical). However, the wide range of values obtained limits the diagnostic value for any one individual. Joint effusions obscure the total amount of biomarkers in affected synovial joints.