TY - JOUR
T1 - GC/TOF-MS-based metabolomic profiling in cultured fibroblast-like synoviocytes from rheumatoid arthritis
AU - Ahn, Joong Kyong
AU - Kim, Sooah
AU - Hwang, Jiwon
AU - Kim, Jungyeon
AU - Kim, Kyoung Heon
AU - Cha, Hoon Suk
PY - 2016
Y1 - 2016
N2 - Objectives: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and hyperplasia. Fibroblast-like synoviocytes (FLS) in RA exhibit a tumor cell-like aggressive phenotype. Thus, gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) was employed to identify the characteristic metabolic profiling of RA FLS. Methods: Metabolite profiling of RA FLS and osteoarthritis (OA) FLS was performed using GC/TOF-MS in conjunction with statistical analyses. We performed metabolite set enrichment analysis to establish which pathways are affected. Results: A total of 129 metabolites were identified. A principal component analysis and hierarchical clustering analysis demonstrated clear differentiation of the metabolic profiling between RA FLS and OA FLS. The levels of 35 metabolites that belonged to the amines, fatty acids, phosphates, and organic acids class were significantly increased in RA FLS compared to those in OA FLS. Also, the levels of 26 metabolites that belonged to the amino acids, sugars, and sugar alcohols class were significantly decreased in RA FLS compared to those in OA FLS. The sugar metabolism (glycolysis and pentose phosphate pathway) and amino acid metabolism (tyrosine and catecholamine biosynthesis, and protein biosynthesis) were severely disturbed in RA FLS compared to those in OA FLS. Conclusions: Our metabolic results suggested that the alteration of sugar metabolism, lipolysis, and amino acid metabolism in RA FLS is related to synovial hyperplasia and inflammation. This is the first metabolomic study to determine metabolic changes characteristic of RA FLS, which will provide valuable information to gain in-depth insights into the pathogenesis of RA.
AB - Objectives: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and hyperplasia. Fibroblast-like synoviocytes (FLS) in RA exhibit a tumor cell-like aggressive phenotype. Thus, gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) was employed to identify the characteristic metabolic profiling of RA FLS. Methods: Metabolite profiling of RA FLS and osteoarthritis (OA) FLS was performed using GC/TOF-MS in conjunction with statistical analyses. We performed metabolite set enrichment analysis to establish which pathways are affected. Results: A total of 129 metabolites were identified. A principal component analysis and hierarchical clustering analysis demonstrated clear differentiation of the metabolic profiling between RA FLS and OA FLS. The levels of 35 metabolites that belonged to the amines, fatty acids, phosphates, and organic acids class were significantly increased in RA FLS compared to those in OA FLS. Also, the levels of 26 metabolites that belonged to the amino acids, sugars, and sugar alcohols class were significantly decreased in RA FLS compared to those in OA FLS. The sugar metabolism (glycolysis and pentose phosphate pathway) and amino acid metabolism (tyrosine and catecholamine biosynthesis, and protein biosynthesis) were severely disturbed in RA FLS compared to those in OA FLS. Conclusions: Our metabolic results suggested that the alteration of sugar metabolism, lipolysis, and amino acid metabolism in RA FLS is related to synovial hyperplasia and inflammation. This is the first metabolomic study to determine metabolic changes characteristic of RA FLS, which will provide valuable information to gain in-depth insights into the pathogenesis of RA.
KW - Amino acid metabolism
KW - Fibroblast-like synoviocytes
KW - Gas chromatography-mass spectrometry
KW - Osteoarthritis
KW - Rheumatoid arthritis
KW - Sugar metabolism
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U2 - 10.1016/j.jbspin.2015.11.009
DO - 10.1016/j.jbspin.2015.11.009
M3 - Article
C2 - 27133762
AN - SCOPUS:84964220613
JO - Revue du Rhumatisme et des Maladies Osteo-Articulaires
JF - Revue du Rhumatisme et des Maladies Osteo-Articulaires
SN - 1169-8330
ER -