Metabolic profile of plasma before and after induction of an isolated intra-articular bone injury in the rabbit knee: Potential to characterize the onset of osteoarthritis?

Background: Surgical models of bone injury-induced joint damage provide relevant insights into the biological pathways involved in the response to injury and development of subsequent degenerative joint conditions. Objective: To determine metabolic changes acutely following a bone injury to the rabbit knee in order to reveal key metabolites potentially associated with the chronic phase post-injury leading to post-traumatic osteoarthritis. Methods: Nine skeletally mature rabbits underwent surgery to create a repeatable, isolated intra-articular bone injury with intraarticular bleeding, without destabilizing the knee. Plasma samples were collected pre-operatively (baseline) and at 3 weeks post-injury. The samples were analyzed using nuclear magnetic resonance spectroscopy-based metabolic profiling approach and multivariate statistical analysis. Results: Metabolic profiling found clear separation between pre-surgical and post-injury rabbits. The predictive ability of the statistical model reached 75%. The levels of twelve metabolites (adenine, choline, glutamine, glycine, pyroglutamate, ornithine, 1-methylhistidine, creatinine, acetate, glucose, taurine and glutamate) significantly changed in plasma samples collected from the rabbits 3 weeks post-injury compared to their baseline levels. Conclusions: Our study indicates that metabolomics may have important applications in the detection of early systemic changes following a localized joint injury, possibly enabling early intervention and preventing progression to more serious joint degeneration.