VDR signaling and macrophages are therapeutic targets for JAK2V617F-driven myelofibrosis. (A-D) WT mice were transplanted with BM from WT (VDR^+/+), VDR^+/+/JAK2V617F Tg (VDR^+/+_JAK), or VDR^−/−/JAK2V617F Tg (VDR^−/−_JAK) mice (n = 2, 9, and 10, respectively). Three months after transplantation, the appearance and size of the spleen (A; scale bars, 2 mm), silver staining of femur sections with enumeration of digitized pictures (B-C; scale bar, 50 μm), and the correlation between the severity of fibrosis and TGF-β1 mRNA expression in the bone tissue including BM (normalized to β-actin; D) were assessed. (E-G) WT mice transplanted with BM from JAK2V617F/MaFIA double Tg mice were treated with AP20187 to deplete macrophages. Three months after transplantation, silver staining of femur sections with enumeration of digitized pictures (E-F) and megakaryocyte numbers (G) were assessed (n = 4-7). Scale bar, 50 μm. Representative pictures or combined data of at least 3 independent experiments are shown. Data are represented as mean plus or minus SEM. **P < .01 (Student t test and Pearson correlation coefficient).