Application of global metabolomic profiling of synovial fluid for osteoarthritis biomarkers.
Osteoarthritis affects over 250 million individuals worldwide. Currently, there are no options for early diagnosis of osteoarthritis, demonstrating the need for biomarker discovery. To find biomarkers of osteoarthritis in human synovial fluid, we used high performance liquid-chromatography mass spectrometry for global metabolomic profiling. Metabolites were extracted from human osteoarthritic (n = 5), rheumatoid arthritic (n = 3), and healthy (n = 5) synovial fluid, and a total of 1233 metabolites were detected. Principal components analysis clearly distinguished the metabolomic profiles of diseased from healthy synovial fluid. Synovial fluid from rheumatoid arthritis patients contained expected metabolites consistent with the inflammatory nature of the disease. Similarly, unsupervised clustering analysis found that each disease state was associated with distinct metabolomic profiles and clusters of co-regulated metabolites. For osteoarthritis, co-regulated metabolites that were upregulated compared to healthy synovial fluid mapped to known disease processes including chondroitin sulfate degradation, arginine and proline metabolism, and nitric oxide metabolism. We utilized receiver operating characteristic analysis to determine the diagnostic value of each metabolite and identified 35 metabolites as potential biomarkers of osteoarthritis, with an area under the receiver operating characteristic curve >0.9. These metabolites included phosphatidylcholine, lysophosphatidylcholine, ceramides, myristate derivatives, and carnitine derivatives. This pilot study provides strong justification for a larger cohort-based study of human osteoarthritic synovial fluid using global metabolomics. The significance of these data is the demonstration that metabolomic profiling of synovial fluid can identify relevant biomarkers of joint disease.
['Carlson|Alyssa K|AK|', 'Rawle|Rachel A|RA|', 'Adams|Erik|E|', 'Greenwood|Mark C|MC|', 'Bothner|Brian|B|', 'June|Ronald K|RK|']
D001172:Arthritis, Rheumatoid D015415:Biomarkers D006801:Humans D055442:Metabolome D055432:Metabolomics D010003:Osteoarthritis D025341:Principal Component Analysis D013582:Synovial Fluid
Metabolomics synovial fluid Osteoarthritis Biomarkers Mass spectrometry principal component analysis rheumatoid arthritis receiver operating characteristic curve Joint disease HCA LC-MS Mass-to-charge ratio OA PCA RA ROC SF hierarchical cluster analysis liquid chromatography mass spectrometry m/z