Figure 3. DOT1L protects against osteoarthritis by preventing Wnt hyper-activation.

(a) Wnt antagonist XAV-939 (XAV) rescues gene expression changes in ACAN, COL2A1 and COL1A1 induced by EPZ-5676 in healthy human articular chondrocytes. Data are from one experiment with three technical replicates. (b,c) C57/Bl6 wild-type mouse knees were injected with EPZ (5 mg kg⁻¹), XAV (0.1 (low dose—L) or 0.5 (high dose—H) mg kg⁻¹) or vehicle and killed after 4 weeks. Knees were sectioned and stained with Hematoxylin-Safranin O (b). Scale bar, 200 μm. Cartilage damage was scored (see Methods section) and is shown in (c). One experiment was performed with n=3 (vehicle, EPZ and XAV-939 only) and n=10 (EPZ+XAV9393 groups). **P<0.01 (two-tailed t-test) compared to EPZ treatment only. All error bars indicate mean±s.e.m.