title: GC/TOF-MS-based metabolomic profiling in cultured fibroblast-like synoviocytes from rheumatoid arthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea.
authors.forename: Joong Kyong
authors.initials: JK
authors.lastname: Ahn
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Sooah
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, National Police Hospital, Seoul 05715, Republic of Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Jungyeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul 02841, Republic of Korea. Electronic address: khekim@korea.ac.kr.
authors.forename: Kyoung Heon
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06531, Republic of Korea. Electronic address: hoonsuk.cha@samsung.com.
authors.forename: Hoon-Suk
authors.initials: HS
authors.lastname: Cha
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D000073893:Sugars / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D000070918:Synoviocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D000596:Amino Acids; D000073893:Sugars
keywords: Amino acid metabolism; Fibroblast-like synoviocytes; Gas chromatography-mass spectrometry; Osteoarthritis; Rheumatoid arthritis; Sugar metabolism