Advances in tooth agenesis and tooth regeneration

Abstract

The lack of treatment options for congenital (0.1%) and partial (10%) tooth anomalies highlights the need to develop innovative strategies. Over two decades of dedicated research have led to breakthroughs in the treatment of congenital and acquired tooth loss. We revealed that by inactivating USAG-1, congenital tooth agenesis can be successfully ameliorated during early tooth development and that the inactivation promotes late-stage tooth morphogenesis in double knockout mice. Furthermore, Anti- USAG-1 antibody treatment in mice is effective in tooth regeneration and can be a breakthrough in treating tooth anomalies in humans. With approximately 0.1% of the population suffering from congenital tooth agenesis and 10% of children worldwide suffering from partial tooth loss, early diagnosis will improve outcomes and the quality of life of patients. Understanding the role of pathogenic USAG-1 variants, their interacting gene partners, and their protein functions will help develop critical biomarkers. Advances in next-generation sequencing, mass spectrometry, and imaging technologies will assist in developing companion and predictive biomarkers to help identify patients who will benefit from tooth regeneration.

Keywords: BMP, bone morphogenetic protein; CEBPB, CCAAT enhancer binding protein beta; Congenital tooth agenesis; EDA; EDA, Ectodysplasin A; Tooth regeneration; USAG-1 neutralizing antibody; USAG-1, Uterine sensitization associated gene-1.

Fig. 1

Timeline of tooth regeneration breakthroughs in Takahashi's lab.

Fig. 2

Picture on the left shows interacting partners of USAG-1 gene with the default settings in STRING ver 11.5. Picture on the right shows USAG-1 interacting partners including SMAD family genes, RUNX2 and others.