Metabolomics of Synovial Fluid and Infrapatellar Fat Pad in Patients with Osteoarthritis or Rheumatoid Arthritis

Petteri Nieminen*, Wilhelmiina Hämäläinen, Juha Savinainen, Marko Lehtonen, Saara Lehtiniemi, Juho Rinta-Paavola, Petri Lehenkari, Tommi Kääriäinen, Antti Joukainen, Heikki Kröger, Tommi Paakkonen, Anne Mari Mustonen

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

12 Citations (Scopus)
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Abstract

Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are inflammatory joint diseases with complex and insufficiently understood pathogeneses. Our objective was to characterize the metabolic fingerprints of synovial fluid (SF) and its adjacent infrapatellar fat pad (IFP) obtained during the same surgical operation from OA and RA knees. Non-targeted metabolite profiling was performed for 5 non-inflammatory trauma controls, 10 primary OA (pOA) patients, and 10 seropositive RA patients with high-resolution mass spectrometry-based techniques, and metabolites were matched with known metabolite identities. Groupwise differences in metabolic features were analyzed with the univariate Welch’s t-test and the multivariate linear discriminant analysis (LDA) and principal component analysis (PCA). Significant discrimination of metabolite profiles was discovered by LDA for both SF and IFP and by PCA for SF based on diagnosis. In addition to a few drug-derived substances, there were 16 and 13 identified metabolites with significant differences between the diagnoses in SF and IFP, respectively. The pathways downregulated in RA included androgen, bile acid, amino acid, and histamine metabolism, and those upregulated included biotin metabolism in pOA and purine metabolism in RA and pOA. The RA-induced downregulation of androgen and bile acid metabolism was observed for both SF and IFP. The levels of 11 lipid metabolites, mostly glycerophospholipids and fatty acid amides, were also altered by these inflammatory conditions. The identified metabolic pathways could be utilized in the future to deepen our understanding of the pathogeneses of OA and RA and to develop not only biomarkers for their early diagnosis but also therapeutic targets.

Original languageEnglish
Pages (from-to)1101-1117
Number of pages17
JournalInflammation
Volume45
Issue number3
Early online date18 Jan 2022
DOIs
Publication statusPublished - Jun 2022
MoE publication typeA1 Journal article-refereed

Keywords

  • high-resolution mass spectrometry
  • joint disease
  • metabolomics
  • osteoarthritis
  • rheumatoid arthritis
  • synovial fluid

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