VEGFA and primary hypertrophic osteoarthropathy: PGE2 induces transcription of the VEGF in osteoblasts and stimulates bone formation, activates endothelial cells that increase transcription of VEGF promoting local angiogenesis, increases capillary permeability, and promotes stimulation and migration of osteoblasts, new bone formation, and edema, all of which account for the characteristic findings in PHO (Zhang et al., 2013), as shown in Figure 3.