Interactions between osteopontin and vascular endothelial growth factor: Implications for skeletal disorders

Osteopontin (OPN) and vascular endothelial growth factor (VEGF) are characterized by a convergence in function for maintaining the homeostasis of the skeletal and renal systems (the bone-renal-vascular axis regulates bone metabolism). The two cytokines contribute to bone remodeling, dental healing, kidney function, and the adjustment to microgravity. Often, they are co-expressed or one molecule induces the other, however, in some settings OPN-associated pathways and VEGF-associated pathways are distinct. In bone remodeling, OPN and VEGF are regulated under the influence of growth factors and hormones, hypoxia and inflammation, the micro-environment, and various physical forces. Their abundance can be affected by drug treatment. OPN and VEGF are variably associated with kidney disease. Their balanced levels are critical for restoring endothelial cell function and ameliorating the adverse effects of microgravity. Here, we review the relevant 83 papers of 257 articles published, and listed in PubMed under the key words OPN and VEGF.