Epithelial Bone Morphogenic Protein 2 and 4 Are Indispensable for Tooth Development.

Haibin Mu,Xiaohua Xie,Xin Liu,Bin Zhang,Heran Chang,Lili Li,Dian Su,Shuoshuo Geng,Ying Li,Han Jin,Xiumei Wang

doi:10.3389/fphys.2021.660644

Abstract

The Bmp2 and Bmp4 expressed in root mesenchyme were essential for the patterning and cellular differentiation of tooth root. The role of the epithelium-derived Bmps in tooth root development, however, had not been reported. In this study, we found that the double abrogation of Bmp2 and Bmp4 from mouse epithelium caused short root anomaly (SRA). The K14-cre;Bmp2f/f;Bmp4f/f mice exhibited a persistent Hertwig’s Epithelial Root Sheath (HERS) with the reduced cell death, and the down-regulated BMP-Smad4 and Erk signaling pathways. Moreover, the Shh expression in the HERS, the Shh-Gli1 signaling, and Nfic expression in the root mesenchyme of the K14-cre;Bmp2f/f;Bmp4f/f mice were also decreased, indicating a disrupted epithelium- mesenchyme interaction between HERS and root mesenchyme. Such disruption suppressed the Osx and Dspp expression in the root mesenchyme, indicating an impairment on the differentiation and maturation of root odontoblasts. The impaired differentiation and maturation of root odontoblasts could be rescued partially by transgenic Dspp. Therefore, although required in a low dosage and with a functional redundancy, the epithelial Bmp2 and Bmp4 were indispensable for the HERS degeneration, as well as the differentiation and maturation of root mesenchyme.

Highlights

The mammalian tooth is putatively regarded as an intact organ to fulfill physiological functions, the enamel-covered tooth crown and the cementum-covered tooth root undergo separated developmental processes which are regulated by different genetic mechanisms (SteelePerkins et al, 2003)
The etiology of short root anomaly (SRA) could arrange from root mesenchyme to epithelial Hertwig’s Epithelial Root Sheath (HERS) (Huang et al, 2012)
With regards to the role of BMP signaling in root development, previous studies demonstrated that Bmps were dominantly expressed in the root mesenchyme (Yamashiro et al, 2003), which was essential for the activation and maintenance of Nuclear Factor I C (Nfic) expression by activating Smad-dependent BMP signaling in HERS (Huang et al, 2010)

Summary

Introduction

The mammalian tooth is putatively regarded as an intact organ to fulfill physiological functions, the enamel-covered tooth crown and the cementum-covered tooth root undergo separated developmental processes which are regulated by different genetic mechanisms (SteelePerkins et al, 2003). The development of tooth crown is divided into laminar, bud, cap, and bell stages according to the morphology of the epithelial-derived enamel organ (Luder et al, 2015). In the tooth germs of bell stage, the enamel organ differentiates into outer enamel epithelium (OEE), HERS BMPs in Root Development satellite reticulum, stratum intermediate, and inner enamel epithelium (IEE) from the external to internal side. At the apical edge of the enamel organ, OEE and IEE meet together to form a bilayer epithelium which elongates into Hertwig’s Epithelial Root Sheath (HERS). The HERS degenerates and disappears in the erupted tooth, instead of differentiating into the enamel-secreting ameloblasts as the IEE does in the crown (Huang et al, 2009). A number of studies demonstrated that both the formation and degeneration of HERS were key to the length, shape, and number of tooth root, as well as the cementum and periodontal ligament (Bosshardt et al, 2015)

Methods

Results

Conclusion