Left Panel: Mesenchymal stem cells (MSCs) are mobilized to DTCs through CXC-chemokine ligand 12 (CXCL12) and release exosomes containing dormancy promoting miRNA or are cannibalized by the DTCs. Inactive endothelial cells release thrombospondin 1 (TSP1) to promote dormancy and reduce proliferation of DTCs. Osteoblasts secrete transforming growth factor (TGF)-β2 and growth differentiation factor 10 (GDF10) to inhibit cellular proliferation, and express leukemia inhibitory factor (LIF) that is recognized by LIF receptor (LIFR) on dormant DTCs.
Right Panel: DTCs express interferon-γ (IFN- γ) that inhibits TSP1 expression in endothelial cells. Active endothelial cells secrete TGF-β1 and periostin to promote DTC proliferation. DTCs secrete vascular cell adhesion protein 1 (VCAM1) to promote maturation and activation of osteoclasts. Graphics adapted from Servier Medical Art (https://smart.servier.com/).