Occurrence, biochemical profile of vascular endothelial growth factor (VEGF) isoforms and their functions in endochondral ossification

Vascular endothelial growth factor (VEGF), initially detected in bovine pituitary follicular cells, is widely localized in hypertrophic zones of chondrocytes in various tissues where focus is on bone growth. Similarly, VEGF found in chondrocytes of articular cartilage of osteo-arthritic/rheumato-arthritic joints reflected need for bone repair. Members of VEGF family of human origin are seven homo-dimeric, heparin-binding glyco-proteins, encoded by different genes located on different chromosomes. They encode seven isoforms: VEGF-A, -B, -C, -D, -E, -F, and PLGF, each catalyzing distinct functions. They are compared with VEGFs derived from bovine origin in biochemical composition and functions. Each isoform and subtype has specific receptors for binding, necessary for expression of specific functions in bone growth or repair. VEGF control is by diffusion of isoforms, hypoxic conditions, and bone (mandibular) positioning. Thus, transformation of cartilage into bone involves proliferation of mesenchymal cells, hypertrophy in chondrocytes, capillary invasion, and calcification by extra cellular matrix (ECM). Inherent limitations of in vitro/in vivo models and chronology of appearance of different isoforms have eluded precise mechanism of VEGF action and regulation. Nonetheless, central role of VEGF in bone growth is quite obvious. J. Cell. Physiol. 227: 1298-1308, 2012. (C) 2011 Wiley Periodicals, Inc.