RNA sequencing analysis reveals distinct gene expression patterns in infrapatellar fat pads of patients with end-stage osteoarthritis or rheumatoid arthritis

Abstract

Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are inflammatory joint diseases that share partly similar symptoms but have different, inadequately understood pathogeneses. Adipose tissues, including intra-articular infrapatellar fat pad (IFP), may contribute to their development. Analysis of differentially expressed genes (DEGs) in IFPs could improve the diagnostics of these conditions and help to develop novel treatment strategies. The aim was to identify potentially crucial genes and pathways discriminating OA and RA IFPs using RNA sequencing analysis. We aimed to distinguish genetically distinct patient groups as a starting point for further translational studies with the eventual goal of personalized medicine. Samples were collected from arthritic knees during total knee arthroplasty of sex- and age-matched OA and seropositive RA patients (n = 5–6/group). Metabolic pathways of interest were investigated by whole transcriptome sequencing, and DEGs were analyzed with univariate tests, hierarchical clustering (HC), and pathway analyses. There was significant interindividual variation in mRNA expression patterns, but distinct subgroups of OA and RA patients emerged that reacted similarly to their disease states based on HC. Compared to OA, RA samples showed 703 genes to be upregulated and 691 genes to be downregulated. Signaling pathway analyses indicated that these DEGs had common pathways in lipid metabolism, fatty acid biosynthesis and degradation, adipocytokine and insulin signaling, inflammatory response, and extracellular matrix organization. The divergent mRNA expression profiles in RA and OA suggest contribution of IFP to the regulation of synovial inflammatory processes and articular cartilage degradation and could provide novel diagnostic and therapeutic targets.