Fig. 6: Schematic representation of the proposed molecular mechanism by which p53 regulates bone remodeling.

Enriched testosterone produced by prostate cancer cells can suppress p53 expression in MSCs. These MSCs with p53 deficiency exhibit more potential to generate osteoblasts and produce OPG. The enhanced OPG production can block the RANKL-RANK signaling in osteoclasts and results in an impairment of bone resorption. Such concerted action modulated by p53 regulates the bone remodeling and constructs the bone metastatic niche of prostate cancer. OPG osteoprotegerin, RANKL receptor activator of nuclear factor κΒ ligand, RANK receptor activator of nuclear factor-κB.