Wise G E, Yao S
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
Crit Rev Eukaryot Gene Expr. 2003;13(2-4):173-80.
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.
牙齿萌出需要牙囊募集单核细胞，这些单核细胞融合形成破骨细胞，破骨细胞吸收牙槽骨，使牙齿能够萌出。在大鼠第一下颌磨牙中，出生后第3天会出现一次主要的破骨细胞生成高峰，第10天会出现一次较小的高峰。诸如集落刺激因子-1（CSF-1）等萌出分子在牙囊中于第3天表达量最高，以促进最大程度的破骨细胞形成，但到破骨细胞生成的第二次高峰时，它们的表达会显著降低。由于血管内皮生长因子（VEGF）可以替代CSF-1来促进破骨细胞生成，我们检测了其在牙囊中的体内基因表达，发现它及其两种主要异构体（VEGF 120和164）在第9 - 11天表达量最高，即第二次高峰出现的时间。用佛波酯肉豆蔻酸酯乙酸盐（PMA，一种蛋白激酶C（PKC）激活剂）处理细胞，可增强培养的牙囊细胞中两种主要VEGF异构体的表达，而添加特异性PKC抑制剂则可阻止这种情况。用PMA处理还会增加VEGF的蛋白水平。因此，VEGF可能参与促进破骨细胞生成的第二次高峰，并且PKC的激活可能会上调其表达。
