Serum branched-chain amino acid to histidine ratio: a novel metabolomic biomarker of knee osteoarthritis

Zhai, Guangju; Wang-Sattler, Rui; Hart, Deborah; Arden, N K; Hakim, Alan J.; Illig, Thomas; Spector, Tim D.

doi:10.1136/ard.2009.120857

Cited by 160 publications

(150 citation statements)

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“…We would also like to note that, while direct comparison of our results to some of the reported findings is difficult as different methods and sample types were used, we did observe an increase in the ratios of valine/histidine, leucine/histidine and isoleucine/histidine for the OA group at week 14, compared to the control group (week 14 sham group) (Supplemental Figure S12), which is consistent with the findings reported by Zhia et al . in the human samples19.…”

Section: Discussionmentioning

confidence: 99%

“…Several metabolomic profiling studies using human subjects and animal models have been reported on the investigation of metabolic responses to OA using biofluids such as urine, plasma and synovial fluids1819202122. Li et al .…”

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confidence: 99%

“…performed targeted analysis of 163 serum metabolites using LC-MS from 123 knee OA cases and 299 controls for initial biomarker discovery with additional 76 knee OA cases and 100 controls for replication study. They found that the ratios of valine to histidine and leucine/isoleucine to histidine could be used to differentiate OA cases from the controls19. Adams et al .…”

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confidence: 99%

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Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

Chen

Wang

et al. 2017

Sci Rep

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We report a chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) method generally applicable for tracking metabolomic changes from samples collected in an animal model for studying disease development and treatment. A rat model of surgically induced osteoarthritis (OA) was used as an example to illustrate the workflow and technical performance. Experimental duplicate analyses of 234 plasma samples were carried out using dansylation labeling LC-MS targeting the amine/phenol submetabolome. These samples composed of 39 groups (6 rats per group) were collected at multiple time points with sham operation, OA control group, and OA rats with treatment, separately, using glucosamine/Celecoxib and three traditional Chinese medicines (Epimedii folium, Chuanxiong Rhizoma and Bushen-Huoxue). In total, 3893 metabolites could be detected and 2923 of them were consistently detected in more than 50% of the runs. This high-coverage submetabolome dataset could be used to track OA progression and treatment. Many differentiating metabolites were found and 11 metabolites including 2-aminoadipic acid, saccharopine and GABA were selected as potential biomarkers of OA progression and OA treatment. This study illustrates that CIL LC-MS is a very useful technique for monitoring incremental metabolomic changes with high coverage and accuracy for studying disease progression and treatment in animal models.

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Section: Discussionmentioning

confidence: 99%

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Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

Chen

Wang

et al. 2017

Sci Rep

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“…Mass spectroscopy has also been used to look for novel biomarkers for knee OA (Zhai et al, 2010). They looked at serum samples of unrelated white women with and without knee OA.…”

Section: Osteoarthritismentioning

confidence: 99%

Metabolomics in the Analysis of Inflammatory Diseases

et al. 2012

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“…This may be due to altered permeability in inflamed tissues and thereby increased influx of fatty acids. In inflammation increased protein breakdown can be judged by the increased levels of essential amino acids as shown by the increased valine levels in patients of osteoarthritis [28]. In Crohn's disease and ulcerative colitis, analysis of fecal extracts showed decreased levels of butyrate, acetate and methylamine [29], suggesting that reduced amounts of gut bacteria may have a role to play in these diseases.…”

Section: Chronic Inflammationmentioning

confidence: 99%

Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases

2014

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To refer to metabolomics as a new field is injustice to ancient doctors who used ants to diagnose the patients of diabetes having glycosuria. Measuring the levels of molecules in biological fluids believing them to be the representatives of biochemical pathways of carbohydrates, fats, proteins, nucleic acids or xenobiotic metabolism and deciphering meaningful data from it is what can be called as metabolomics, just as high glucose in urine suggests diabetes mellitus. Genomics, epigenetics, proteomics, transcriptomics finally converge to metabolomics, which are the signatures of mechanisms of bodily processes which is why understanding this science can have many applications. Just as a heap of stones does not make a house, having data of metabolite levels does not make it a science. Analyzing this data would help us in constructing biochemical pathways and their interactions. Analyzing the changes caused by a drug in the metabolite levels would help us in deriving the mechanisms by which the drug acts. Comparing metabolite levels in diseased with non-diseased, good-responders with poor-responders to a particular drug can help in identifying new markers of a disease or response to a drug respectively. Also, metabolite levels of an endogenous substrate can tell us the status of a person's metabolizing enzymes and help in drug dose titration. Generating hypothesis by identifying the new molecular markers and testing their utility in clinics seems to be the most promising approach in future. This review narrates the modes of quantifying and identifying metabolome, its proposed applications in diagnosis, monitoring and understanding the diseases and drug responses. We also intend to identify hindrances in using metabolomics in clinical studies or experiments.

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Serum branched-chain amino acid to histidine ratio: a novel metabolomic biomarker of knee osteoarthritis

Abstract: This is the first serum-based metabolomic study of osteoarthritis in humans. The branched-chain amino acids to histidine ratio has potential clinical use as an osteoarthritis biomarker and shows the clinical potential of metabolomics.

Cited by 160 publications

References 24 publications

Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

Metabolomics in the Analysis of Inflammatory Diseases

Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases

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