Metabolomic profiles of induced pluripotent stem cells derived from patients with rheumatoid arthritis and osteoarthritis

Metabolomic profiles of induced pluripotent stem cells derived from patients with rheumatoid arthritis and osteoarthritis

Metabolomics is the systemic study of the unique fingerprints of metabolites involved in cellular processes and biochemical reactions. The metabolomic approach is useful in diagnosing and predicting the development of rheumatoid arthritis (RA) and osteoarthritis (OA) and is emerging as a useful tool...

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Published in:Stem cell research & therapy Vol. 10; no. 1; p. 319
Main Authors: Kim, Juryun, Kang, Sunyoung Christina, Yoon, Na Eun, Kim, Yena, Choi, Jinhyeok, Park, Narae, Jung, Hyerin, Jung, Byung Hwa, Ju, Ji Hyeon
Format: Journal Article
Language:English
Published: England BioMed Central Ltd 15-11-2019
BioMed Central
BMC
Subjects:
Analysis
Arthritis
ATP (Adenosine triphosphate)
Biological markers
Criminal investigation
Diagnosis
Enzymes
Fibroblast-like synoviocytes
Induced pluripotent stem cells
Metabolites
Metabolomics
Muscle proteins
Niacinamide
Nicotinamide
Osteoarthritis
Physiological aspects
Rheumatoid arthritis
Rheumatoid factor
Scientific equipment industry
Spectroscopy
Stem cells
United States
Tannic acid
Metabolomics
Induced pluripotent stem cells
Rheumatoid arthritis
Fibroblast-like synoviocytes
Nicotinamide
Osteoarthritis
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Summary:Metabolomics is the systemic study of the unique fingerprints of metabolites involved in cellular processes and biochemical reactions. The metabolomic approach is useful in diagnosing and predicting the development of rheumatoid arthritis (RA) and osteoarthritis (OA) and is emerging as a useful tool for identifying disease biomarkers. The aim of this study was to compare the metabolic blueprint of fibroblast-like synoviocyte (FLS) cells and induced pluripotent stem cells (iPSCs) derived from RA and OA patients. Somatic cells of RA patients (n = 3) and OA patients (n = 3) were isolated, transduced with a lentiviral plasmid, and reprogrammed into iPSCs displaying pluripotency. Metabolic profiling of RA and OA patient-derived FLS cells and iPSCs was performed using liquid chromatography/mass spectrometry and statistical analysis. After normalization by the sum of the peak intensities through LC/MS, 37 metabolites were detected across RA and OA patients. The metabolites of RA and OA were distinguishable according to the PLS-DA analysis. LysoPC (20:4), 4-methoxychalcone, phosphorylcholine, and nicotinamide (NAM) were significantly higher in RA iPSCs than in OA iPSCs (p < 0.05). The NMNAT-3 enzyme, which catalyzes an important step in the biosynthesis of NAD from adenosine triphosphate, was also upregulated in RA iPSCs. Interestingly, the proliferation of RA iPSCs was significantly greater than OA iPSC proliferation (p < 0.05). NAM played a critical role in the proliferation of RA iPSCs but not in OA iPSCs. When iPSCs were treated with 100 nM of the NAM inhibitor tannic acid (TA), the proliferation of RA iPSCs was significantly reduced (p < 0.001). The metabolites of RA and OA FLS cells and RA and OA iPSCs were all clearly distinguishable from each other. NAM played a critical role in the proliferation of RA iPSCs but not in OA iPSCs. TA effectively inhibited the expression of NAM in RA iPSCs and is a possible effective treatment for RA patients.
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ISSN:1757-6512
1757-6512
DOI:10.1186/s13287-019-1408-5