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
N1 - Funding Information:
This work was supported by the Advanced Biomass R&D Center of Korea (2011-0031353), the National Research Foundation of Korea funded by the Ministry of Education (NRF-2013R1A1A2059103), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare (HI14C2285), which are funded by the Korean government. Experiments were performed using the facilities of the Institute of Biomedical Science and Food Safety at the Korea University Food Safety Hall.
Publisher Copyright:
© 2016 Société française de rhumatologie
PY - 2016/12/1
Y1 - 2016/12/1
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
UR - http://www.scopus.com/inward/record.url?scp=84964220613&partnerID=8YFLogxK
U2 - 10.1016/j.jbspin.2015.11.009
DO - 10.1016/j.jbspin.2015.11.009
M3 - Article
C2 - 27133762
AN - SCOPUS:84964220613
VL - 83
SP - 707
EP - 713
JO - Joint Bone Spine
JF - Joint Bone Spine
SN - 1297-319X
IS - 6
ER -