FIGURE 2.

Schematic diagram of the cell cross-talk between OS and OC cell line. Mononuclear macrophages derived from bone marrow differentiate into POC induced by receptors for MCSF and RANKL, and subsequently multiple POC fuse into OC in response to MCSF and RANKL. POC may promote OS growth and metastasis by secreting cytokines and regulating angiogenesis. MCSF and RANKL produced by OS directly and indirectly stimulate OC differentiation and maturation, and differentiated and mature OC further stimulate OS growth by releasing growth factors and minerals during bone resorption, such as IGF1 or TGF-β. RANK-containing exosomes secreted by OC may act on RANKL expressed on OS cells to promote OS progression through RANK-RANKL reverse signaling. The arrow represents the direction, the dotted line represents the unproven, and the solid line represents the proven.