Histomorphological Changes of Mouse Tooth Germs by Antisense Inhibition of Krox-25 are S imilar to the Deranged Proliferation of Odontogenic Tumors
Krox-25, a Kruppel type zinc finger protein, may play an important role for the morphogenesis of tooth in ectomesenchymal interaction between enamel epithelium and odontogenic mesenchyme. The interrupted expression of Krox-25 by antisense inhibition is supposed to affect the abnormal development of tooth germ similar to the deranged proliferation of odontogenic tumors. This study was performed to know the histomorphogenetic effect of Krox-25 antisense inhibition in tooth germs of mouse embryos and to understand the abnormal expressions of Krox-25 in different odontogenic tumors which proliferate in aberrant direction of ecto-mesenchymal interaction. Total 95 tooth germs obtained from pregnant mice in the 13th day of fertilization were cultured with antisense oligonucleotides targeting mouse Krox-25 gene, and their histological patterns were compared with those of different odontogenic tumors, i.e., ameloblastic fibro-odontoma (n=5), ameloblastoma (n=8), and ameloblastic carcinoma (n=2). Resultantly, the cultured tooth germs treated with antisense oligodeoxynucleotides produced primitive dentine and enamel by odontoblasts and ameloblasts, respectively, but they aberrantly grew and formed abnormal tooth organs. Especially, the harmonious growth of enamel and dentine formation was greatly deranged by the antisense inhibition in the organ culture system. These findings were much similar to the abnormal growth of odontogenic tumors. The relatively well differentiated enamel epithelium of ameloblastic fibro-odontoma showed irregularly strong reaction of Krox-25, while the poorly differentiated enamel epithelium of ameloblastic carcinoma showed weak reaction. These data suggest that Krox-25 may play important roles for the histomorphogenesis of tooth germ by signaling the ecto-mesenchymal interaction between odontoblasts and ameloblasts in normal tooth germ development of mouse embryos as well as in cytodifferentiation of odontogenic tumors.