Differences in the composition of hip and knee synovial fluid in osteoarthritis: a nuclear magnetic resonance (NMR) spectroscopy study of metabolic profiles

Abstract

Objective: The hip and knee joints differ biomechanically in terms of contact stresses, fluid lubrication and wear patterns. These differences may be reflected in the synovial fluid (SF) composition of the two joints, but the nature of these differences remains unknown. The objective was to identify differences in osteoarthritic hip and knee SF metabolites using metabolic profiling with Nuclear Magnetic Resonance (NMR) spectroscopy. Design: Twenty-four SF samples (12 hip, 12 knee) were collected from patients with end-stage osteoarthritis (ESOA) undergoing hip/knee arthroplasty. Samples were matched for age, gender, ethnicity and had similar medical comorbidities. NMR spectroscopy was used to analyse the metabolites present in each sample. Principal Component Analysis and Orthogonal Partial Least Squares Discriminant Analysis were undertaken to investigate metabolic differences between the groups. Metabolites were identified using 2D NMR spectra, statistical spectroscopy and by comparison to entries in published databases. Results: There were significant differences in the metabolic profile between the groups. Four metabolites were found in significantly greater quantities in the knee group compared to the hip group (N-acetylated molecules, glycosaminoglycans, citrate and glutamine). Conclusions: This is the first study to indicate differences in the metabolic profile of hip and knee SF in ESOA. The identified metabolites can broadly be grouped into those involved in collagen degradation, the tricarboxylic acid cycle and oxidative metabolism in diseased joints. These findings may represent a combination of intra and extra-articular factors.

Nuclear magnetic resonance spectroscopy of biofluids for osteoarthritis

“…Akhbari et al. 26 conducted NMR analysis on human clinical samples of hip and knee OA and found citrate, n-acetylated molecules, glutamine and glycosaminoglycans to be differentially abundant in and in greater quantities in the knee group compared to hip. Citrate is an intermediate in the TCA cycle, as well as urea, amino acid and fatty acid metabolism.…”

“…Citrate is an intermediate in the TCA cycle, as well as urea, amino acid and fatty acid metabolism. 26 Altered energy production and oxidative metabolism have been regarded as characteristic of OA. 26 Glutamine was associated with altered oxidative metabolism as well suppressing the formation of cytokines and protecting chondrocytes from heat stress.…”

“…GAGs have also been regularly associated with cartilage breakdown. 26 Anderson et al. 27 observed differences between OA and rheumatoid arthritis (RA) in clinical human synovial fluid samples.…”

LC-MS-Based Metabolomics Analysis Revealed Deleterious Effect of Infrapatellar Fat Pad on Articular Chondrocytes of Osteoarthritis

“…The increased levels of citric acid and succinic acid and decreased levels of isocitrate in the culture medium OA chondrocytes after treatment of FCM indicate enhanced activity of the TCA cycle, possibly due to perturbed metabolism in the cartilage cells. Akhbari et al's [15] study on synovial uid (SF) showed that when compared with the metabolites of the SF in rheumatoid arthritis patients, OA patients had higher levels of metabolites involved in both TCA and glycolysis. Another study examined the metabolites of SFs between early-and late-stage OA and found that TCA intermediate metabolites including malate, citrate, succinate, and fumarate levels were signi cantly higher in the late-stage OA group than in the early-stage OA group, suggesting that the upregulation of the TCA pathway is greater in the late stage of OA [16].…”

“…Glutamine is a precursor of glucosamine and can upregulate glucosamine synthesis in chondrocytes, and glucosamine could inhibit cartilage destruction and promote biosynthetic activity of chondrocytes [27]. A study observed that the concentration of glutamine was lower in the SF from OA patients than in normal SF [15]. In addition, 2-keto-glutaramic acid (a deaminated metabolite of glutamine under abnormal conditions) has been found to be increased in the urine of in ammatory OA participants, indicating that glutamine metabolism might be disturbed in the chondrocytes [28].…”