Histomorphological Changes of Mouse Tooth Germs by Antisense Inhibition of Krox-25 are Similar to the Deranged Proliferation of Odontogenic Tumors

다국어 초록 (Multilingual Abstract)

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.

참고문헌 (Reference)

1 Migaldi M, "Tumor cell proliferation and microsatellite alterations in human ameloblastoma" 44 : 50-60, 2008

2 Gibson CW, "Transgenic mice that express normal and mutated amelogenins" 86 : 331-335, 2007

3 Gao Y, "The human KROX- 26/ZNF22 gene is expressed at sites of tooth formation and maps to the locus for permanent tooth agenesis (He-Zhao deficiency)" 82 : 1002-1007, 2003

4 Sonoda A, "The critical role of heparin binding domains of ameloblastin for dental epithelium cell adhesion and ameloblastoma proliferation" 2009

5 Sorkin BC, "The cadherin- catenin complex is expressed alternately with the adenomatous polyposis coli protein during rat incisor amelogenesis" 48 : 397-406, 2000

6 Je G. Chi, "The Structure of the Rat Ameloblastin Gene and Its Expression in Amelogenesis" 한국분자세포생물학회 15 (15): 216-225, 2003

7 Nakano K, "Notch signaling in benign and malignant ameloblastic neoplasms" 13 : 476-480, 2008

8 Kruse AL, "New classification of maxillary ameloblastic carcinoma based on an evidence-based literature review over the last 60 years" 1 : 31-, 2009

9 Bei M, "Molecular genetics of ameloblast cell lineage" 312B : 437-444, 2009

10 Lee SK, "Molecular cloning, chromosomal mapping, and characteristic expression in tooth organ of rat and mouse Krox-25" 83 : 243-253, 200

11 Ganss B, "Krox-26 is a novel C2H2 zinc finger transcription factor expressed in developing dental and osteogenic tissues" 43 : 161-166, 2002

12 Wilkinson DG, "In Situ Hybridization: A Practical Approach" Oxford University Press 1992

13 Fukumoto S, "Essential roles of ameloblastin in maintaining ameloblast differentiation and enamel formation" 181 : 189-195, 2005

14 Zhang L, "Epithelial expression of SHH signaling pathway in odontogenic tumors" 42 : 398-408, 2006

15 Teo W, "Developmental expression pattern and DNA-binding properties of the zinc finger transcription factor Krox-26" 44 (44): 161-166, 2003

16 Gruenbaum-Cohen Y, "Amelogenin in cranio-facial development: the tooth as a model to study the role of amelogenin during embryogenesis" 312B : 445-457, 2009

17 Nascimento J, "Ameloblastic fibro-odontoma: a conservative surgical approach" 2009

18 Cavalcante AS, "Ameloblastic fibro-odontoma: a case report" 2009

19 Naik V, "Ameloblastic carcinoma: a case report" 38 : 873-879, 2007

20 Tanaka TS, "A global view of gene expression in the preimplantation mouse embryo: morula versus blastocyst" 115 (115): S85-S91, 2004