Gas chromatography-time of flight/mass spectrometry-based metabonomics of changes in the urinary metabolic profile in osteoarthritic rats.

The aim of the present study was to explore changes in the urinary metabolic spectrum in rats with knee osteoarthritis, using gas chromatography-time of flight/mass spectrometry (GC-TOF/MS) to determine the metabonomic disease pathogenesis. Sprague-Dawley rats were randomly divided into the control and model groups (n=8/group), and 20 µl of 4% papain and 0.03 M L-cysteine was injected into the right knee on days 1, 3 and 7 to establish the knee osteoarthritis model. Following 14 days, urine was collected over 12 h and cartilage ultrastructural damage was assessed by hematoxylin-eosin staining. GC-TOF/MS, combined with principal component analysis, partial least squares discriminant modeling and orthogonal partial least squares discriminant modeling, was used to analyze the changes in the metabolic spectrum trajectory and to identify potential biomarkers and their related metabolic pathways. Compared with the control group, the synovial cell lining of the knee joint exhibited proliferation, inflammatory cell infiltration and collagen fiber hyperplasia in the knee osteoarthritis group. A total of 23 potential biomarkers were identified, including alanine, α-ketoglutarate, asparagine, maltose and glutamine. Furthermore, metabolomic pathogenesis of osteoarthritis may be related to disorders of amino acid metabolism, energy metabolism, fatty acid metabolism, vitamin B6 metabolism and nucleic acid metabolism.