A systematic review of the small molecule studies of osteoarthritis using nuclear magnetic resonance and mass spectroscopy

Abstract

s u m m a r yObjective: To perform a systematic review of the small molecule metabolism studies of osteoarthritis utilising nuclear magnetic resonance (NMR) or mass spectroscopy (MS) analysis (viz., metabolomics or metabonomics), thereby providing coherent conclusions and reference material for future study. Method: We applied PRISMA guidelines (PROSPERO 95068) with the following MESH terms: 1. "osteoarthritis" AND ("metabolic" OR "metabonomic" OR "metabolomic" OR "metabolism") 2. ("synovial fluid" OR "cartilage" OR "synovium" OR "serum" OR "plasma" OR "urine") AND ("NMR" or "Mass Spectroscopy"). Databases searched were "Medline" and "Embase". Studies were searched in English and excluded review articles not containing original research. Study outcomes were significant or notable metabolites, species (human or animal) and the NewcastleeOttawa Score. Results: In the 27 studies meeting the inclusion criteria, there was a shift towards anaerobic and fatty acid metabolism in OA disease, although whether this represents the inflammatory state remains unclear. Lipid structure and composition was altered within disease subclasses including phosphatidyl choline (PC) and the sphingomyelins. Macromolecular proteoglycan destruction was described, but the correlation to disease factors was not demonstrated. Collated results suggested arachidonate signalling pathways and androgen sex hormones as future metabolic pathways for investigation. Conclusion: Our meta-analysis demonstrates significant small molecule differences between sample types, between species (such as human and bovine), with potential OA biomarkers and targets for local or systemic therapies. Studies were limited by numbers and a lack of disease correlation. Future studies should use NMR and MS analysis to further investigate large population subgroups including inflammatory arthropathy, OA subclasses, age and joint differences.Crown

Fatty Acids and Oxylipins in Osteoarthritis and Rheumatoid Arthritis—a Complex Field with Significant Potential for Future Treatments

“…Both OA and RA are characterized by altered lipid metabolism, and lipids have been proposed to play several roles in their pathogeneses [ 7 – 9 ]. Increased body fat mass is a risk factor for OA development, as it induces mechanical stress, especially in the tibiofemoral joint, and causes systemic low-grade inflammation [ 10 , 11 ].…”

The Small Molecule Components of Human Synovial Fluid and Bovine Calf Serum that Correlate with Cobalt Chrome (CoCrMo) Wear

“…Furthermore, the lipid peaks in 25BCS provided stronger NMR peaks from the (CH 2 ) n moiety (41). Higher levels of choline and 3hydroxyisobutyrate in the 25BCS samples suggest a destruction of complex lipid species and fatty acid metabolism (50). Alternatively, it could indicate a high level of gluconeogenesis.…”

“…The presence of active joint in ammation reduces the oxygen tension and yields an anaerobic state (48,49). Animal studies of osteoarthritic synovial uid compared to healthy controls found an elevation in anaerobic metabolism, fatty acid chain oxidation and proteoglycan degradation (50). The free oxygen of bovine and human arterial blood is similar(51, 52).…”

“…The presence of proteoglycan in the HSF is supported, although not con rmed, by the observation of the N-acetyl moiety (2.03ppm). A larger N-acetyl signal has been indicative of proteoglycan destruction, including hyaluronan (50). Free amino acids alanine, glutamine, leucine and valine were elevated in the HSF compared to the 25BCS model, possibly due to proteinolysis.…”

The Metabolome and Osteoarthritis: Possible Contributions to Symptoms and Pathology

“…As metabolites can be used as biomarkers, circulating metabolites or those in urine may be indicative of underlying pathologies. There are a vast number of metabolite changes that have been identified in both blood and synovial fluid of OA patients [13], suggesting that metabolites could influence the various OA pathological features or associated comorbidities in both the local disease environment and in distant organs.…”