Kim, Juryun Kang, Sunyoung Christina Yoon, Na Eun Kim, Yena Choi, Jinhyeok Park, Narae Jung, Hyerin Jung, Byung Hwa Ju, Ji Hyeon 2024-01-19T18:34:35Z 2024-01-19T18:34:35Z 2021-09-05 2019-11-15 1757-6512 https://pubs.kist.re.kr/handle/201004/119321 Background 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. Methods 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. Results 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). Conclusions 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. English BMC FIBROBLAST-LIKE SYNOVIOCYTES SYNOVIAL-FLUID BIOMARKERS APOPTOSIS INFLAMMATION EXPRESSION INDUCTION REVEALS TANNINS TARGETS NAD(+) Metabolomic profiles of induced pluripotent stem cells derived from patients with rheumatoid arthritis and osteoarthritis Article 10.1186/s13287-019-1408-5 1 STEM CELL RESEARCH & THERAPY, v.10, no.1 STEM CELL RESEARCH & THERAPY 10 1 scie scopus 000497705400001 2-s2.0-85075114956 Cell & Tissue Engineering Cell Biology Medicine, Research & Experimental Cell Biology Research & Experimental Medicine Article FIBROBLAST-LIKE SYNOVIOCYTES SYNOVIAL-FLUID BIOMARKERS APOPTOSIS INFLAMMATION EXPRESSION INDUCTION REVEALS TANNINS TARGETS NAD(+) Metabolomics Rheumatoid arthritis Osteoarthritis Induced pluripotent stem cells Fibroblast-like synoviocytes Nicotinamide Tannic acid