Metabolomic analysis of human plasma reveals that arginine is depleted in knee osteoarthritis patients

Zhang, W.; Sun, Guang; Likhodii, Sergei; Liu, M.; Aref‐Eshghi, Erfan; Harper, Patricia E.; Martin, Glynn; Furey, Andrew; Green, R.; Randell, Edward; Rahman, Proton; Zhai, Guangju

doi:10.1016/j.joca.2015.12.004

Cited by 96 publications

(112 citation statements)

References 35 publications

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“…Metabolic profiling using synovial fluid collected from 55 knee OA patients and 13 cadaveric controls, revealed 11 metabolites that separated the two groups 41 . None of the 11 metabolites identified in synovial fluid matched those found in the urine samples from our progression study or those found in plasma samples from a cross-sectional study of knee OA 20 .…”

Section: Discussioncontrasting

confidence: 71%

“…All prior metabolomic studies in humans have been cross-sectional in nature comparing individuals with or without OA using either urine 18, 40 , serum 19 , synovial fluid 41 or plasma 20 . An NMR-based urine metabolomics study that used samples from the Johnston County Osteoarthritis project found differences in participants with radiographic hip or knee OA from controls and noted a correlation of a metabolite profile with radiographic OA severity 18 .…”

Section: Discussionmentioning

confidence: 99%

“…In a similar approach using plasma samples, patients with knee OA were found to have lower levels of arginine 20 . Finally, a metabolomics study that examined serum samples from healthy controls and patients with osteoarthritis, rheumatoid arthritis (RA), ankylosing spondylitis and gout, found that the patients with arthritis could be differentiated from the controls and that each form of arthritis had a distinct metabolite profile 42 .…”

Section: Discussionmentioning

confidence: 99%

“…We sought to determine if a profile of metabolites could be found that distinguished progressors from non-progressors. A few cross-sectional studies have reported a different metabolomic profile between individuals with and without knee OA 18–20 but an association of metabolites with disease progression in people with established OA has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study

Loeser

Pathmasiri

Sumner

et al. 2016

Osteoarthritis and Cartilage

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Summary Introduction Metabolic factors may contribute to osteoarthritis (OA).This study employed metabolomics analyses to determine if differences in metabolite profiles could distinguish people with knee OA who exhibited radiographic progression. Methods Urine samples obtained at baseline and 18 months from overweight and obese adults in the Intensive Diet and Exercise for Arthritis (IDEA) trial were selected from two subgroups (n=22 each) for metabolomics analysis: a group that exhibited radiographic progression (≥ 0.7mm decrease in joint space width, JSW) and an age, gender, and BMI matched group who did not progress (≤0.35mm decrease in JSW). Multivariate analysis methods, including orthogonal partial least square discriminate analysis, were used to identify metabolite profiles that separated progressors and non-progressors. Plasma levels of IL-6 and C-reactive protein were evaluated as inflammatory markers. Results Multivariate analysis of the binned metabolomics data distinguished progressors from non-progressors. Library matching revealed that glycolate, hippurate, and trigonelline were among the important metabolites for distinguishing progressors from non-progressors at baseline whereas alanine, N,N-dimethyglycine, glycolate, hippurate, histidine, and trigonelline, were among the metabolites that were important for the discrimination at 18 months. In non-progressors, IL-6 decreased from baseline to 18 months while IL-6 was unchanged in progressors; the change over time in IL-6 was significantly different between groups. Conclusion These findings support a role for metabolic factors in the progression of knee OA and suggest that measurement of metabolites could be useful to predict progression. Further investigation in a larger sample that would include targeted investigation of specific metabolites is warranted.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study

Loeser

Pathmasiri

Sumner

et al. 2016

Osteoarthritis and Cartilage

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“…Within this study, arginine levels were initially identified as decreased following treatment at the earliest time point. A recent study of human plasma also identified arginine to be depleted in knee OA 75 . The authors proposed this is due to an increased activity of the conversion of arginine to ornithine resulting in an imbalance between cartilage repair and degradation.…”

Section: Discussionmentioning

confidence: 94%

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

Anderson

Phelan

Foddy

et al. 2020

Preprint

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Osteoarthritis (OA) is an age-related degenerative musculoskeletal disease characterised by loss of articular cartilage, synovitis, abnormal bone proliferation and subchondral bone sclerosis. Underlying OA pathogenesis is yet to be fully elucidated with no OA specific biomarkers in clinical use. Ex-vivo equine cartilage explants (n=5) were incubated in TNFα/IL-1β supplemented culture media for 8 days, with media removed and replaced at 2, 5 and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent 1D 1 H nuclear magnetic resonance metabolomic analysis with media samples also undergoing mass spectrometry proteomic analysis.Within the cartilage, metabolites glucose and lysine were elevated following TNF-α/IL-1β treatment whilst adenosine, alanine, betaine, creatine, myo-inositol and uridine levels decreased. Within the culture media, four, four and six differentially abundant metabolites and 154, 138 and 72 differentially abundant proteins, with > 2 fold change, were identified for 1-2 day, 3-5 day and 6-8 day time points respectively. Nine potential novel OA neopeptides were elevated in treated media. Our innovative study has identified differentially abundant metabolites, proteins and extracellular matrix derived neopeptides, providing insightful information on OA pathogenesis, enabling potential translation for clinical markers and possible new therapeutic targets.

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Metabolomics in chronic pain research

Teckchandani

Gowda

Raftery

et al. 2020

European Journal of Pain

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Background and ObjectiveMetabolomics deals with the identification and quantification of small molecules (metabolites) in biological samples. As metabolite levels can reflect normal or altered metabolic pathways, their measurement provides information to improve the understanding, diagnosis and management of diseases. Despite its immense potential, metabolomics applications to pain research have been sparse. This paper describes current metabolomics techniques, reviews published human metabolomics pain research and compares successful metabolomics research in other areas of medicine with the goal of highlighting opportunities offered by metabolomics to advance pain medicine.Databases and Data TreatmentNon‐systematic review.ResultsOur search identified 19 studies that adopted a metabolomics approach in: fibromyalgia (7), chronic widespread pain (4), other musculoskeletal pain conditions (5), neuropathic pain (1), complex regional pain syndrome (1) and pelvic pain (1). The studies used either mass spectrometry or nuclear magnetic resonance. Most are characterized by small sample sizes. Some consistency has been found for alterations in glutamate and testosterone metabolism, and metabolic imbalances caused by the gut microbiome.ConclusionsMetabolomics research in chronic pain is in its infancy. Most studies are at the pilot stage. Metabolomics research has been successful in other areas of medicine. These achievements should motivate investigators to expand metabolomics research to improve the understanding of the basic mechanisms of human pain, as well as provide tools to diagnose, predict and monitor chronic pain conditions. Metabolomics research can lead to the identification of biomarkers to support the development and testing of treatments, thereby facilitating personalized pain medicine.

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Metabolomic analysis of human plasma reveals that arginine is depleted in knee osteoarthritis patients

Abstract: Arginine is significantly depleted in refractory knee OA patients. Further studies within a longitudinal setting are required to examine whether arginine can predict early OA changes.

Cited by 96 publications

References 35 publications

Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study

Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study

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

Metabolomics in chronic pain research

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