Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging therapeutic targets

Figure 1 Phases of bone remodeling. Starting from the quiescence phase, bone remodeling is triggered by different stimuli that lead to activation of lining cells, which increase surface expression of receptor activator of nuclear factor kappa-B ligand (RANKL). This cytokine, by binding to its receptor RANK, promotes osteoclast differentiation (activation phase). Next, mature osteoclasts resorb bone (resorption phase), thus allowing the release of factors usually stored in the bone matrix (BMPs, TGF-β and FGFs) that recruit osteoblasts in the reabsorbed area. Once recruited, osteoblasts form the bone matrix and ensure its mineralization (formation phase), completing the bone remodeling process. BMPs: Bone morphogenetic proteins; TGF-β: Transforming growth factor-β; FGFs: Fibroblast growth factor; OCL: osteoclast; OBL: osteoblast.