¹H NMR Metabolomics Identifies Underlying Inflammatory Pathology in Osteoarthritis and Rheumatoid Arthritis Synovial Joints

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.

Impaired chondrocyte U3 snoRNA expression in osteoarthritis impacts the chondrocyte protein translation apparatus

“…Little is known about the control www.nature.com/scientificreports/ of snoRNA transcription from dedicated transcriptional units, but our group previously reported that transcriptional activity of another dedicated snoRNA gene (RMRP) can also be influenced via major chondrocyte signaling pathways during chondrogenesis 39 . OA synovial fluid is a complex body fluid containing a plethora of catabolic morphogens and cytokines/chemokines 40,41 . Therefore we expect that the signaling molecule composition of OA synovial fluid acts on major chondrocyte signaling pathways, leading to the observed decreased U3 snoRNA expression.…”

1H-NMR-Based Analysis for Exploring Knee Synovial Fluid Metabolite Changes after Local Cryotherapy in Knee Arthritis Patients

“…It is used to assess and quantify a wide variety of metabolites in order to correctly diagnose diseases and reveal new therapeutic avenues [ 20 , 21 , 22 ]. This approach has been previously used to assess the metabolite profiles of knee-joint synovial fluid obtained from patients with knee arthritis [ 23 , 24 , 25 ] or from animal models of osteoarthritis [ 26 , 27 ]. The present study may provide novel insights into the underlying molecular pathways involved in cryotherapy’s antioxidative and anti-inflammatory effects.…”

Ex-VivoEquine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study

“…1 H Nuclear magnetic resonance (NMR) metabolomics analysis provides a high level of technical reproducibility with a minimal level of sample preparation 38 . 1 H NMR analysis has previously been used to investigate OA in the SF of humans, horses, pigs and dogs 9,[39][40][41][42][43][44][45] . Synovial metabolites alanine, choline, creatine and glucose have been identified as differentially abundant in OA across multiple studies and species 9,39,[41][42][43][44] .…”

“…1 H NMR analysis has previously been used to investigate OA in the SF of humans, horses, pigs and dogs 9,[39][40][41][42][43][44][45] . Synovial metabolites alanine, choline, creatine and glucose have been identified as differentially abundant in OA across multiple studies and species 9,39,[41][42][43][44] . NMR techniques have also previously been used to characterise cartilage with high resolution magical angle spinning (HRMAS) NMR utilised to assess enzymatic degradation of bovine cartilage [46][47][48] .…”