Abstract
Despite osteoarthritis (OA) and rheumatoid arthritis (RA) being typically age-related, their underlying etiologies are markedly different. We used 1H nuclear magnetic resonance (NMR) spectroscopy to identify differences in metabolite profiles in low volumes of OA and RA synovial fluid (SF). SF was aspirated from knee joints of 10 OA and 14 RA patients. 100 μL SF was analyzed using a 700 MHz Avance IIIHD Bruker NMR spectrometer with a TCI cryoprobe. Spectra were analyzed by Chenomx, Bruker TopSpin and AMIX software. Statistical analysis was undertaken using Metaboanalyst. 50 metabolites were annotated, including amino acids, saccharides, nucleotides and soluble lipids. Discriminant analysis identified group separation between OA and RA cohorts, with 32 metabolites significantly different between OA and RA SF (false discovery rate (FDR) < 0.05). Metabolites of glycolysis and the tricarboxylic acid cycle were lower in RA compared to OA; these results concur with higher levels of inflammation, synovial proliferation and hypoxia found in RA compared to OA. Elevated taurine in OA may indicate increased subchondral bone sclerosis. We demonstrate that quantifiable differences in metabolite abundance can be measured in low volumes of SF by 1H NMR spectroscopy, which may be clinically useful to aid diagnosis and improve understanding of disease pathogenesis.
Highlights
Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common forms of arthritis, which lead to significant disability and substantial reduction in quality of life.[1,2] Despite both these chronic conditions being typically age-related with insidious onset, their underlying etiologies are markedly different.[3,4] OA is a degenerative joint condition, primarily affecting the hands, hips and knees, with one-third of people in the UK aged over 45 requiring treatment.[5]
We have identified OA synovial fluid (SF) to be enriched in a number of proteins including S100-A10, Collagen type I and CD109.9 RA is a systemic, inflammatory autoimmune disease that primarily affects the synovium of joints,[10] presenting as a symmetric polyarthritis with an estimated prevalence of 0.5−1% of the adult population within developed countries.[11,12]
Metabolomic studies in OA and RA have focused on biofluids, including urine, serum and SF using a number of different platforms including gas chromatography−mass spectrometry (GC−MS), liquid chromatography−mass spectrometry (LC−MS) and 1H nuclear magnetic resonance (NMR) spectroscopy.[19,22,27−37] These studies have provided insight into the metabolites found within human arthritic SF, and the different underlying cellular pathology of OA and RA
Summary
Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common forms of arthritis, which lead to significant disability and substantial reduction in quality of life.[1,2] Despite both these chronic conditions being typically age-related with insidious onset, their underlying etiologies are markedly different.[3,4] OA is a degenerative joint condition, primarily affecting the hands, hips and knees, with one-third of people in the UK aged over 45 (approximately 8.75 million) requiring treatment.[5]. We have identified OA synovial fluid (SF) to be enriched in a number of proteins including S100-A10, Collagen type I and CD109.9 RA is a systemic, inflammatory autoimmune disease that primarily affects the synovium of joints,[10] presenting as a symmetric polyarthritis with an estimated prevalence of 0.5−1% of the adult population within developed countries.[11,12] RA joints
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