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. 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.