Figure 5

P53 status and the vicious cycle between BME and OS. In a p53 mutational landscape, BME components represent a soil for tumor promotion. In this scenario, p53-null MSCs exhibit higher proliferation rate, impaired osteogenesis, and altered immunoregulatory properties such as higher expression levels of iNOS (inducible nitric oxide synthase), CCL5, IL-6, and TGF-β. These molecules can, in turn, stimulate bone tumor-forming cells to produce cytokines to support their growth and affect BME. This generates a vicious cycle of cross-talking between BME and OS, which is dictated from p53 status