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Fig. 11. Two distinct roles of VEGFA during endochondral bone formation are
regulated by different pathways. Diagram showing major components of the
pathways that regulate expression of Vegfa in hypertrophic
chondrocytes (right) and epiphyseal chondrocytes (left) during endochondral
ossification. Angiogenesis into hypertrophic cartilage and establishment of
the primary ossification center in developing long bones depend on a high
level of Vegfa expression, controlled by the transcription factor
Runx2, in hypertrophic chondrocytes
(Zelzer et al., 2001). Since a
reduction in the level of Vegfa was also observed in Ctgf
null mice (Ivkovic et al.,
2003), it is possible that Runx2 and Ctgf may be components of two
independent or dependent regulatory pathways for control of Vegfa
expression. In epiphyseal cartilage, cell survival depends on expression of
Vegfa at a moderate level under the control of HIF1 and von
Hippel-Lindau (VHL) protein. Whether Vegfa is the only critical
target gene for HIF1 regulation in this chondrocyte survival pathway is not
known, and it is possible that other genes may also play a role.
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