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

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

doi:10.1007/s10753-021-01604-x

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.

Highlights

Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are degenerative joint diseases that cause significant morbidity and a high demand for health services, including pain medication, rehabilitation, and surgery [1, 2]
The primary OA (pOA) and RA patients were significantly older than the C group, and the pOA patients had higher average body mass index (BMI) compared to the RA group
Volcano plots show that multiple molecular features could clearly separate both RA and pOA synovial fluid (SF) from C SF (Fig. 1A–B, D–E), but differences between RA and pOA were more modest in both SF and infrapatellar fat pad (IFP) (Fig. 1C, F and 2)

Summary

Introduction

Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are degenerative joint diseases that cause significant morbidity and a high demand for health services, including pain medication, rehabilitation, and surgery [1, 2]. While both OA and RA are considered inflammatory diseases, RA synovial tissue is characterized by higher immune cell infiltration and cytokine expression [3]. In order to discover new targets for disease prevention, early diagnosis, and pain management, it is crucial to assess the biochemical correlates and metabolic pathways related to subjective pain and disease prognosis. Diagnosis of joint diseases would be of pivotal importance, as substantial and irreversible joint pathology is usually present by the time of diagnosis

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