Resolution of inflammation in imprinted fibroblast-like synoviocytes establishes a transcriptomic signature that promotes endothelial cell dysfunction.

Purpose: We analyzed RNA-seq from fibroblast-like synoviocytes obtained from TNF induced inflammatory arthritis mice. Our goal was to evaluate the gene expression signatures after the cessation of inflammatory conditions. Methods: We analyzed bulk RNA-seq from fibroblast-like synoviocytes from TNF induced inflammatory arthritis mice in diferent conditions: homeostasis (5% sucrose water for 3 weeks), inflammation (1mg/ml Doxycycline + 5% sucrose water for 3 weeks), resolution (1mg/ml Doxycycline + 5% sucrose water for 3 weeks and then stopped for next 3 weeks). Samples were sequenced to determine transcriptional changes and regulated processes. Results: paired-end reads were mapped to the mus musculus GRCm38.p3 genome assembly. RNA levels were normalized by RPKM and student's t-test. Conclusion: Despite the resolution of the inflammatory phase of arthritis, fibroblast-like synoviocytes showed a clear persistence of inflammatory transcriptomic expression. Our study highlighted that the persistent aggressive phenotype of fibroblast-like synoviocytes not only promotes inflammation and exacerbates joint damage but also triggers impaired endothelial cell functioning. Overall design: Investigation of the possible mechanisms underlying the endothelial cell dysfunction induced by activated fibroblast-like synoviocytes in the resolution phase of TNF-induced inflammatory arthritis.