Characterization of synovial fluid metabolomic phenotypes of cartilage morphological changes associated with osteoarthritis

Abstract

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 ¼ 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.

Irisin Mitigates Oxidative Stress, Chondrocyte Dysfunction and Osteoarthritis Development through Regulating Mitochondrial Integrity and Autophagy

“…The histopathological features were that defective autophagy and oxidative damage in chondrocytes were present in patients with end-stage knee OA and in mice with DMM-mediated knee joint injury. The analyses were in agreement with other groups' studies showing that oxidative stress [40] and autophagy loss [8,41] are correlated with the severity and development of human knee OA. Autophagy failure escalates apoptotic programs in osteoarthritic chondrocytes; however, very little is known about the regulatory mechanism underlying these deleterious reactions.…”

Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations

“…Because of the higher prevalence of asymptomatic OA, it is approximated that 250 million people all over the world suffer from OA [ 8 , 9 ]. The prevalence of knee OA increased significantly over the last decades and continues to rise, partially because of the increasing prevalence of obesity and other risk factors, but also independently, of other causes [ 10 ].…”

Differential correlation network analysis identified novel metabolomics signatures for non-responders to total joint replacement in primary osteoarthritis patients

“…However, as the previous analysis used an individual metabolite-based analytic method with a conservative significance level, we might miss other important markers that play a role in TJR response. Metabolomics has previously been used to show distinct metabolic phenotypes of OA patients (Carlson et al 2019) and thus offers a valuable technique to identify non-responders, especially when used with a network approach. Network science is a powerful tool to investigate the relationships and interaction patterns of a set of entities and has seen many applications to biomedical research as these types of analyses do not require a priori hypotheses and can thus be used to identify datadriven subgroups in complex disease that otherwise may not have been considered due to the large number of factors often considered in these types of analyses and lack of known relationship between factors.…”