Figure 7.

Schematic of S1P-dependent cross talk between osteoblasts and bone marrow endothelial cells acting in an autocrine and paracrine manner to stimulate bone growth. S1P stimulates VEGFa production in osteoblasts via S1PR3 to increase bone mass in an autocrine and H-type vessel formation in a paracrine manner. To this end, S1P induces VEGFa production through S1PR3 signaling in OBs that leads to autocrine stimulation of OB differentiation and calcification. In addition, secreted VEGFa stimulates angiogenesis and the generation of osteogenic H-type vessels that promote osteoblastogenesis by secreting osteogenic factors such as Pdgfa, Pdgfb, and Tgfb1. Furthermore, S1P directly stimulates OB differentiation through S1PR2 signaling as shown before.⁹