Type II/III Runx2/Cbfa1 is required for tooth germ development

• Published in: Bone (New York, N.Y.) Vol. 38; no. 6; pp. 836 - 844
• Main Authors: Kobayashi, Ieyoshi, Kiyoshima, Tamotsu, Wada, Hiroko, Matsuo, Kou, Nonaka, Kazuaki, Honda, Jun-ya, Koyano, Kiyoshi, Sakai, Hidetaka
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2006
• Subjects: Animals; Antisense oligonucleotide; Core Binding Factor Alpha 1 Subunit - classification; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Dental Enamel Proteins - genetics; Extracellular Matrix Proteins - genetics; Female; Gene Expression; Isoform; Male; Mice; Mice, Inbred BALB C; Organ culture; Organ Culture Techniques; Phosphoproteins; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Precursors - genetics; Runx2/Cbfa1; Sialoglycoproteins; Tooth Germ - cytology; Tooth Germ - metabolism; Tooth germ development; Isoform; Antisense oligonucleotide; Tooth germ development; Runx2/Cbfa1; Organ culture
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2005.10.026

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.