The vicious cycle of osteoblastic bone metastasis. In the vicious cycle of osteoblastic bone metastasis, cancer cells secrete factors that induce angiogenesis and differentiation of MSCs to osteoblasts. Cancer cells utilize the perivascular niches offered by the sprouting endothelium. Osteoblasts induce differentiation and activation of osteoclasts, and growth factors released by bone resorption support the growth of tumor cells. Abbreviations: BMPs: bone morphogenetic proteins, FGFs: fibroblast growth factors, MSC: mesenchymal stem cell, PDGF: platelet-derived growth factor, ET-1: endothelin 1, TGF-β: transforming growth factor β, IGF: insulin-like growth factor.