title: Type II/III Runx2/Cbfa1 is required for tooth germ development.
abstract: Runx2/Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation. Runx2/Cbfa1 knockout mice showed both a complete lack of ossification and the developmental arrest of tooth germ. We here report Runx2/Cbfa1 isoform-type specific functional roles in the development of tooth germ by the administration of antisense phosphorothioate oligodioxynucleotides (S-ODNs) into cultured mouse mandibles. The administration of type II/III Runx2/Cbfa1 antisense S-ODNs into the culture media resulted in an arrest of tooth germ growth at the bud-like stage in cultured mandible taken from the 11-day-old embryos, while also causing the inhibition of the differentiation of odontogenic cells into ameloblast and odontoblast in cultured tooth germs taken from the 15-day-old embryos. The expression of dentin matrix protein 1, dentin sialophosphoprotein, amelogenin, and ameloblastin was shown to be markedly suppressed in cultured tooth germ by the semi-quantitative RT-PCR. Meanwhile, no developmental arrest of tooth germ, no inhibition of gene expression, or differentiation of odontogenic cells was observed in samples treated with the type I Runx2/Cbfa1 antisense S-ODNs. The same findings were also observed in either the control or the sense and random sequence S-ODNs-treated samples. These data indicate that the type II/III Runx2/Cbfa1 isoform is closely related to the development and differentiation of tooth germ.
authors.affiliation: Laboratory of Oral Pathology and Medicine, Faculty of Oral Science, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Ieyoshi
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kiyoshima
authors.forename: Hiroko
authors.initials: H
authors.lastname: Wada
authors.forename: Kou
authors.initials: K
authors.lastname: Matsuo
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nonaka
authors.forename: Jun-ya
authors.initials: JY
authors.lastname: Honda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Koyano
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000818:Animals; D050659:Core Binding Factor Alpha 1 Subunit / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D003746:Dental Enamel Proteins / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D010750:Phosphoproteins; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics; D012795:Sialoglycoproteins; D014083:Tooth Germ / Q000166:cytology* / Q000378:metabolism*; D000099311:Dentin Sialophosphoprotein
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D003746:Dental Enamel Proteins; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D011498:Protein Precursors; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C490890:Ambn protein, mouse; C513308:Dmp1 protein, mouse