Assessment of the utility of biomarkers of osteoarthritis in the guinea pig.
OBJECTIVE: To identify biochemical markers of osteoarthritis (OA) in the guinea pig, we characterized four biomarkers and 17 cytokines for age- and strain-related differences. METHODS: Two guinea pig strains were examined in this study: (1) the Hartley (OA-prone) and (2) Strain 13 (OA-resistant). Levels of synovial fluid keratan sulfate (KS) and cartilage oligomeric matrix protein (COMP), as well as levels of serum C2C, CPII, and a panel of cytokines and chemokines were quantified in both guinea pig strains. These included: IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-17, G-CSF, GM-CSF, IFN-gamma, KC, MIP-1 alpha, RANTES, and TNF-alpha. RESULTS: Synovial fluid concentrations of KS and COMP increased coincident with histological OA and correlated positively with the severity of histological damage in both strains. Synovial fluid concentrations of these biomarkers were elevated in the knees of the Hartley compared to the Strain 13 animals, as early as 2 months of age. From as early as 4 months of age, the levels of serum C2C/CPII, representing the ratio of type II collagen degradation and synthesis, were elevated in the OA-prone Hartley compared with Strain 13 animals. Also, at 12 months of age, strain-related differences were apparent for 11 of the 16 cytokines and chemokines. Using multiple linear regression, serum IL-6 and TNF-alpha concentrations were each strongly associated with strain, weight, and their interaction (r2 = 0.80, P = 0.0002 for IL-6; r2 = 0.55, P = 0.02 for TNF-alpha). CONCLUSIONS: Biomarkers derived from synovial fluid are reflective of histological severity in the spontaneous model of OA in the guinea pig. The synovial fluid biomarker profiles indicated accelerated cartilage matrix turnover in the Hartley strain as early as 2 months of age, prior to evidence of histological damage. The Hartley strain also exemplified an imbalance in type II collagen metabolism and a serum cytokine/chemokine profile indicative of a pro-inflammatory state. These findings elucidate additional disease-related features in the guinea pig that have relevance to OA in humans.
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