Multiple functional involvement of Thymosin beta-4 in tooth germ development

Abstract

Thymosin beta-4 (Tβ4) is known to be ubiquitously involved in the actin monomer sequestering on the cytoskeleton. Our previous study showed specific temporal and special in situ expression pattern of Tβ4 mRNA in dental epithelial and mesenchymal cells in the developing tooth germ of the mouse lower first molar. In this study, we examined the functional implications of Tβ4 in the developmental course of the mouse lower first molar. An inhibition assay using Tβ4 antisense sulfur-substituted oligodeoxynucleotide (AS S-ODN) in cultured embryonic day 11.0 (E11.0) mandibles showed a significant growth inhibition of the tooth germ. However, no growth arrest of the cultured E15.0 tooth germ was observed by using Tβ4 AS S-ODN. The Tβ4 knockdown led to significantly decreased expression levels of type II/III runt-related transcription factor 2 (Runx2) and nucleolin (Ncl) in the cultured E11.0 mandibles. Since our previous studies proved that the inhibition of type II/III Runx2 and Ncl translations resulted in the developmental arrest of the tooth germ in the cultured E11.0 mandible, Tβ4 appears to play roles in tooth germ development via the regulation of the type II/III Runx2 and Ncl expressions. Tβ4 knockdown also resulted in decreased secretion of matrix metalloproteinase (Mmp)-2, a reduced cell motility activity and upregulation of E-cadherin in dental epithelial mDE6 cells. These results suggest that Tβ4 plays multiple functional roles in odontogenic epithelial cells in the early stages of tooth germ development by regulating the expression of odontogenesis-related genes.

Expression of Thymosin β4 in Ameloblasts during Mouse Tooth Development

“…Tβ4-overexpressing mice show amelogenesis imperfecta due to the reduction in cell polarity caused by the inhibition of actin polymerization that is required for enamel matrix secretion in and migration of presecretory ameloblasts (Cha et al, 2010). In addition, reduction in Runx2 expression by the suppression of Tβ4 mRNA expression inhibits enamel mineralization by downregulating ameloblastin and amelogenin (Kobayashi et al, 2006;Ookuma et al, 2013). Insulin-like growth factor-I (IGF-I) and IGF-II increase enamel deposition by increasing amelogenin and enamelin expression (Catón et al, 2005).…”

The expression and function of thymosin beta 10 in tooth germ development

“…Previous studies (Akhter et al, 2005;Ookuma et al, 2013) demonstrated that Tb4, another member of the beta-thymosin family, participates in the morphogenesis of the tooth germ. However, the in situ expression pattern of Tb10 apparently differs from that of Tb4.…”

“…The DM was either the "DP and follicle" in the cultured explants showing the normal cap-like tooth germ or the "odontogenic ectomesenchyme" in the explants exhibiting an inhibition of tooth germ development (Figs. 7 and 8) (Takahashi et al, 2010;Ookuma et al, 2013).…”

“…Successful insemination was determined based on the presence of a postcopulatory plug in the vagina 12 h later. The embryonic day E0.5 was defined by the presence of the vaginal plug (Takahashi et al, 2010;Ookuma et al, 2013).…”

“…Tb10 inhibits the cell migration of human endothelial cells (Mu et al, 2006). In contrast, Tb4 promotes cell migration by producing matrix metalloproteinase and downregulating E-cadherin (Wang et al, 2003;Ookuma et al, 2013). In addition, Tb10 is expressed in embryonic organs and modulates embryological development (Lin et al, 1990;Hall 1991;Gerosa et al, 2010;Fanni et al, 2011).…”