Publisher Summary This chapter discusses the developmental roles of vascular endothelial growth factor (VEGF) in skeletal morphogenesis, speculates on the future directions of research in this area, and describes some of the challenges in the field. VEGF regulates osteoclastic differentiation, migration, and activity. VEGF is, therefore, a key coordinator of the entire process. VEGF is necessary for osteoclastic activity both at the stage when the primary ossification center is established and later during bone growth. A number of studies have led to the identification of VEGF as a critical factor for the survival of chondrocytes. Several factors with important roles in regulating bone formation also induce the expression of VEGF by osteoblasts. Prostaglandins E1 and E2, BMP-4, BMP-6, BMP-7, FGF-2, TGF-β, endothelin-1, IGF-1, and vitamin D3 can all induce VEGF expression in osteoblasts by activating a variety of signaling pathways. Bone fractures can heal in two divergent ways, similar to the two ways of forming bone during embryonic development. Stabilized fractures heal by intramembranous ossification, and unstable fractures undergo endochondral ossification. The similarity between the embryonic bone development and repair of fractured bones, coupled with the finding that VEGF is expressed at sites of bone fracture, suggests that VEGF is involved in bone repair as it is in bone development.
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