Figure 6.

Inducible ablation of Yap in Pdgfrα-expressing fibroblasts reduces inflammatory arthritis severity. Adult Yap^fl/fl (Yap WT) or Pdgfrα-CreER;Yap^fl/fl (Yap ciKO) mice received tamoxifen to activate Cre and KO Yap, prior to induction of AIA in one knee, with the contralateral knee serving as control. Histological analysis was performed 9 days after arthritis induction. See online supplemental table 3 for mouse genotypes, sex and age. (A) Yap expression in the inflamed synovium detected by IHC with haematoxylin counterstain. Histological images were selected from the same mice as shown in panel (C). Boxed areas in images on the left are shown at higher magnification on the right. Scale bars: 50 µm. For isotype negative control staining, see online supplemental figure 10f. (B) Yap expression in synovium, based on IHC staining intensity. P value indicates result of two-tailed unpaired t-test (WT: n=9; ciKO n=6; pooled data from two experiments). (C) Synovitis and erosive damage in AIA knees detected by H&E staining. Images show matched control and AIA knees from female mice in the same experiment with arthritis scores (WT: 5.00; ciKO: 2.99) close to the average of their respective groups. Boxed areas in images on the left are shown at higher magnification on the right. Scale bars: 200 µm. (D) Histological assessment of severity of synovial hyperplasia, immune infiltrates, cellular exudate and marginal erosions (all on scale 0–3), and overall arthritis severity (scale 0–12). P values indicate results of Mann-Whitney U test (WT: n=9; ciKO: n=6, pooled data from two experiments). Lines and error bars on all graphs indicate mean±95% CI. AIA, antigen-induced arthritis; S, synovium; WT, wild type; Yap, Yes-associated protein.