Depletion of macrophages prevents myelofibrosis in the basic model. (A-B) Silver and H&E staining in femur sections of VDR^−/− recipient mice transplanted with VDR^+/+ BM that were treated with clodronate liposome (1 month after transplantation). Silver staining of the metaphysis was digitized to distinguish fibrosis (blue), trabecular bone (red), and hematopoietic area (yellow; A) and enumerated as the ratio of each area (B; n = 6-8). Scale bars, 500 μm (black) and 50 μm (white). (C) Proposed concept of the basic model. Differentiation of immature hematopoietic cells is skewed toward macrophages, which likely drives myofibroblasts (and also osteoblasts presumably) as collagen producers, leading to myelofibrosis and osteosclerosis. Morphological marrow fibroblasts are composed of both macrophages and myofibroblasts. Representative pictures or combined data of at least 3 independent experiments are shown. Data are represented as mean plus or minus SEM. ***P < .001 (ANOVA).