The role of the TGF-β1 signaling pathway in the process of amelogenesis

Abstract

Amelogenesis is a highly regulated process involving multiple signaling pathways, among which the transforming growth factor-β1 (TGF-β1) signaling pathway plays a pivotal role in enamel formation. This review firstly elucidates the critical functions of TGF-β1 in regulating ameloblast behavior and enamel development, encompassing ameloblast proliferation, differentiation, apoptosis, enamel matrix protein synthesis, and mineralization. Secondly, based on emerging evidence, we further discuss potential interactions between TGF-β signaling and circadian regulation in enamel formation, although this relationship requires further experimental validation. Finally, future research directions are proposed to further investigate the relationship between TGF-β1 and the circadian clock in the context of amelogenesis.

Keywords: TGF-β1; ameloblast; amelogenesis; circadian clock; enamel development; enamel formation.

FIGURE 1

TGF-β classical signaling pathway. Activated TGF-β1 combines with TGFBR1 and TGFBR2 to form a complex. TGFBR2 phosphorylates and activates TGFBR1. The activated TGFBR1 binds to SMAD2 and SMAD3 and phosphorylates them. Phosphorylated SMAD2 and SMAD3 combine with SMAD4 to form a trimer complex. The complex is transported to the nucleus and jointly regulates the expression of specific genes with other transcription factors, co-activators, and co-inhibitors.

FIGURE 2

The TGF-β1 signaling pathway plays multiple roles in amelogenesis. The TGF-β1 regulates (A) proliferation, (B) differentiation and (C) apoptosis of ameloblasts. TGF-β1 also regulates in (D) enamel matrix (AMELX, AMBN and ENAM) synthesis and (E–H) mineralization (MMP20, KLK4, AMTN, endocytosis of ameloblasts and ion transporters).