To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient

Figure 1 Model of the differentiation and migration of osteoclasts precursor myeloid lineage progenitor cells and osteoblasts precursor mesenchymal stem cells in response to sphingosine-1-phosphate gradient. Pre-osteoblast cells express sphingosine-1-phosphate (S1P)₂ to repress it chemotaxis towards platelet derived growth factor (PDGF). After bone morphogenetic protein 2 (BMP2)- induced differentiation of pre-osteoblasts (OB) to OB, S1P₂ is down-regulated to resume the chemotaxis to PDGF. The migration of osteoclasts (OC) precursor myeloid linage progenitor cells to blood system is mediated by the S1P₁ receptor. During receptor activator for nuclear factor κB ligand (RANKL)-induced OC differentiation, S1P₁ expression is suppressed to favor the local bone localization and bone remodeling.