The significant role of glycosaminoglycans in tooth development

Abstract

This review delves into the roles of glycosaminoglycans (GAGs), integral components of proteoglycans, in tooth development. Proteoglycans consist of a core protein linked to GAG chains, comprised of repeating disaccharide units. GAGs are classified into several types, such as hyaluronic acid, heparan sulfate, chondroitin sulfate, dermatan sulfate, and keratan sulfate. Functioning as critical macromolecular components within the dental basement membrane, these GAGs facilitate cell adhesion and aggregation, and play key roles in regulating cell proliferation and differentiation, thereby significantly influencing tooth morphogenesis. Notably, our recent research has identified the hyaluronan-degrading enzyme Transmembrane protein 2 (Tmem2) and we have conducted functional analyses using mouse models. These studies have unveiled the essential role of Tmem2-mediated hyaluronan degradation and its involvement in hyaluronan-mediated cell adhesion during tooth formation. This review provides a comprehensive summary of the current understanding of GAG functions in tooth development, integrating insights from recent research, and discusses future directions in this field.

Keywords: extracellular matrix; glycosaminoglycan; hyaluronic acid; proteoglycan; tooth development.

Fig. 1

Expression patterns of GAG related molecule during tooth development. This figure illustrates the complex interplay between the oral epithelium and the underlying mesenchyme, which is crucial for tooth development.

Fig. 2

The expression of Tmem2 in mouse molar during tooth development. In situ hybridization on transverse paraffin sections at P0 (A) and P14 (B) shows distinct and robust expression at developing molar ameloblasts (white arrowheads) around stratum intermedium, and odontoblasts (open arrowheads). Panel (1) and (2) are enlarged images of boxed areas in (B). (C) To detect HA and Tmem2 protein localization, sagittal sections of mouse molar at P14 were double labeled with an anti-Flag antibody and biotinylated hyaluronic acid binding protein (HABP), with nuclear counterstaining was performed with DAPI. The sagittal section of a P14-aged Tmem2-Flag-knock-in mouse revealed strong expression of Tmem2-FLAG protein (green) on the apical side of ameloblasts, and its expression at the basal end of ameloblasts. In contrast HA (Red) immunoreactivity was detected in the stratum intermedium cells and the mesenchymal tissue surrounding the ameloblasts. For detailed information on the materials and methods used, please refer to Nag et al. 2023. ab, alveolar bone; am, ameloblasts; ca, cervical area; d, dentin; dp, dental pulp; e, enamel; m, mesenchyme; od, odontoblasts.

Fig. 3

The potential roles of Tmem2 in enamel formation. Tmem2 protein localization at the apical and basal end of secretory ameloblasts and in the stratum intermedium. Tmem2 plays border function at the basal end of ameloblasts by inhibiting HA accumulation in ameloblasts. This figure was adapted from Nag et al. 2023, journal of dental research. Description of the figure and any modifications made. Reprinted with permission.