Figure 1. Upregulation of the epigenetic regulator Uhrf1 in arthritis tissue.

(A) Protocol for analysis of collagen antibody-induced arthritis (CAIA) model. PBS (Ctrl^P) or LPS (Ctrl^L) was administered as a control. (B) PCA using microarray data obtained from ankle tissue. (C) Heatmap of differentially expressed gene probes in ankle tissue (log₂FC > |1|, P < 0.01). Log₁₀ transformed read counts are scaled from 1.0 to 3.0. (D) Expression of genes related to epigenetic regulation classified by GSEA. Log₁₀ transformed read counts are scaled to minimum to maximum values. (E) Relative probe counts detected in CAIA ankle compared with Ctrl^P or Ctrl^L ankles. (F) RT-qPCR of Uhrf1 mRNA expression in CAIA (n = 4) and STA (n = 3) ankles. (G) UHRF1 mRNA expression in synovium biopsies from healthy individuals, patients with OA, and patients with RA by RNA-Seq. Data are registered in the Gene Expression Omnibus (GEO GSE89408). (H) Left, representative images of immunofluorescence staining for Uhrf1 (red); Pdpn, Fap, Thy-1, CD45, F4/80, and CD3 (green); and DAPI (blue) in WT STA ankle tissue. Scale bar: 50 μm. Right, quantification of Uhrf1⁺ marker cells in hyperplastic synovium. Cell number in 1 field per similar region of independent mice was calculated. (I) Uhrf1 mRNA expression in SFs treated with 20 ng/mL Tnf-α for 24 hours. Mean ± SD is shown. *P < 0.05 and **P < 0.01 by ANOVA followed by Tukey’s test in F (left), G, and H, and unpaired t test in F (right) and I. Data in A–F and H–I were obtained from 3 to 5 independent experiments.