Expression of vascular endothelial growth factor in the dental follicle.

Tooth eruption requires the presence of the dental follicle to recruit mononuclear cells, which fuse to form osteoclasts that resorb the alveolar bone such that the tooth can erupt. In the rat first mandibular molar, there is a major burst of osteoclastogenesis at day 3 postnatally and a lesser burst at day 10. Eruption molecules, such as CSF-1, are maximally expressed at day 3 in the dental follicle to promote this maximal osteoclast formation, but by the time of the secondary burst of osteoclastogenesis their expression is dramatically reduced. Because vascular endothelial growth factor (VEGF) can substitute for CSF-1 to promote osteoclastogenesis, we examined its gene expression in vivo in the dental follicle and found that it and its two major isoforms (VEGF 120 and 164) were all maximally expressed at days 9-11, the time of the secondary burst. Treatment of the cells with phorbolmyristate acetate (PMA), a protein kinase C (PKC) activator, enhanced expression of the 2 major VEGF isoforms in the cultured dental follicle cells, whereas adding a specific PKC inhibitor prevented this. Treatment with PMA also increased the protein level of VEGF. Thus, VEGF may be involved in promoting the secondary burst of osteoclastogenesis, and activation of PKC may upregulate its expression.