Characterization of synovial fluid metabolomic phenotypes of cartilage morphological changes associated with osteoarthritis.
- Carlson, Alyssa K. [ Montana State University: Mechanical & Industrial Engineering ]
- Rawle, Rachel A. [ Montana State University: Microbiology & Cell Biology ]
- Wallace, Cameron W. [ Montana State University: Health & Human Development ]
- Brooks, E.G. [ Montana State University: Chemical & Biological Engineering ]
- Adams, E. [ Montana State University: Mechanical & Industrial Engineering ]
- Greenwood, Mark C. [ Montana State University: Mathematical Sciences ]
- Olmer, M. [ The Scripps Research Institute, Department of Molecular and Experimental Medicine ]
- Lotz, M. K. [ The Scripps Research Institute, Department of Molecular and Experimental Medicine ]
- Bothner, Brian [ Montana State University: Chemistry & Biochemistry ]
- June, Ronald K. [ Montana State University: Mechanical & Industrial Engineering ]
Objective Osteoarthritis (OA) is a multifactorial disease with etiological heterogeneity. The objective of this study was to classify OA subgroups by generating metabolomic phenotypes from human synovial fluid. Design Post mortem synovial fluids (n = 75) were analyzed by high performance-liquid chromatography mass spectrometry (LC-MS) to measure changes in the global metabolome. Comparisons of healthy (grade 0), early OA (grades I-II), and late OA (grades III-IV) donor populations were considered to reveal phenotypes throughout disease progression. Results Global metabolomic profiles in synovial fluid were distinct between healthy, early OA, and late OA donors. Pathways differentially activated among these groups included structural deterioration, glycerophospholipid metabolism, inflammation, central energy metabolism, oxidative stress, and vitamin metabolism. Within disease states (early and late OA), subgroups of donors revealed distinct phenotypes. Synovial fluid metabolomic phenotypes exhibited increased inflammation (early and late OA), oxidative stress (late OA), or structural deterioration (early and late OA) in the synovial fluid. Conclusion These results revealed distinct metabolic phenotypes in human synovial fluid, provide insight into pathogenesis, represent novel biomarkers, and can move toward developing personalized interventions for subgroups of OA patients.