Expression of thymosin β4 in odontoblasts during mouse tooth development

Abstract

Abstract. Thymosin β4 (Tβ4) is expressed in developing tissue, where it stimulates cell differentiation and migration. Further, Tβ4 is expressed during molar development in mice, but the expression and function of Tβ4 in odontoblasts during mammalian tooth development have not yet been reported. Therefore, this study examined the expression and function of Tβ4 in differentiating odontoblasts during tooth development. As observed by immunohistochemistry, Tβ4 was expressed in the oral epithelium and inside cells of the tooth bud on embryonic day 15 (E15). Further, on E17, Tβ4 was expressed strongly in the dental lamina and oral epithelium, but only expressed in part of the cells in the outer and inner dental epithelium. Tβ4 was strongly expressed in the entire cytoplasm of odontoblasts on postnatal day 1 (PN1) and expressed intensively in the apical area of odontoblasts on PN4. Further, expression of Tβ4 was increased gradually in odontoblasts from PN1 to PN21. In an odontoblast cell line, MDPC-23, expression of Tβ4 mRNA and protein was increased strongly on day 4 and gradually decreased from day 14. The gene expression of dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP), osteocalcin (OCN), osteonectin (ON), and collagen type I, related with mineralization, was significantly decreased in si-Tβ4/MDPC-23 during differentiation compared to that in MDPC-23 cells. Taken together, our results suggest that Tβ4 may be involved in oral epithelial cell proliferation at the initial stage of tooth development and regulates the expression and secretion of proteins during odontoblast differentiation.

The Role of Thymosin Beta 4 on Odontogenic Differentiation in Human Dental Pulp Cells

“…This result differs from that in a study on MDPC-23 cells [13], which showed that Tβ4 mRNA and protein was strongly increased after 4 days and decreased from 14 to 28 days during differentiation of MDPC-23 cells, which might be related to differences in cell types or species and culture conditions.…”

“…Our results indicate that inhibition of Tβ4 by siRNA in HDPCs decreased ALP activity, mineralized nodule formation, and upregulated the expression of mRNAs encoding odontoblastic markers, including ON, OPN, OCN, DSPP, and DMP1. These results are consistent with previous data obtained using the odontoblast-like cells MDPC-23 [13]. Furthermore, activation of Tβ4 by exogenously added Tβ4 peptide in HDPCs increased OM-induced odontoblastic differentiation in a dose-dependent manner.…”

“…In addition, gene expression of DSPP, BSP, OCN, ON, and collagen type I related to mineralization is significantly decreased when Tβ4 is inhibited in the odontoblast-like cells MDPC-23 by Tβ4 siRNA [13]. Moreover, we recently reported that Tβ4-overexpressing transgenic mice promote abnormal hair growth and tooth development as observed by abnormally shaped white teeth and dull incisors [14].…”

Thymosin Beta-4 Suppresses Osteoclastic Differentiation and Inflammatory Responses in Human Periodontal Ligament Cells

“…Exogenous β4 peptide inhibited osteogenic differentiation but facilitated adipogenic differentiation in human bone marrow-derived-mesenchymal stem cells (MSCs) [ 16 ]. In contrast, Tβ4 inhibition by Tβ4 siRNA attenuated odontoblastic differentiation in the odontoblast-like cells, MDPC-23 [ 17 ]. Moreover, we recently demonstrated that odontoblastic differentiation was enhanced by activation of Tβ4 by Tβ4 peptide but was decreased by Tβ4 siRNA in human dental pulp cells (HDPCs) [ 18 ].…”

Cloning comeback

“…Sooam researchers have also created new models for diabetes by putting genes that cause symptoms of the disease in mice into cloned pigs 6 and dogs 7 . Likewise, says Insung Hwang, a transgenic beagle at Sooam that carries a gene related to Alzheimer's disease shows hallmarks of the disease.…”