# USAG‐1 and Regenerative Dentistry, Therapeutic Implications and Future Directions: Review of the Literature

## TL;DR

This paper reviews how inhibiting the USAG-1 gene can promote tooth regeneration and its potential for future dental therapies.

## Contribution

The paper highlights the novel therapeutic potential of USAG-1 inhibition in regenerative dentistry and its preclinical and clinical progress.

## Key findings

- USAG-1 inhibition activates BMP-mediated morphogenesis and promotes tooth regeneration in preclinical models.
- Monoclonal antibodies targeting USAG-1 show promise in treating congenital tooth agenesis and promoting third dentition.
- RNA-seq analysis confirms USAG-1 expression in secretory cells of kidney, jaw, and gingiva.

## Abstract

Uterine Sensitization‐Associated Gene 1 (USAG‐1) is a bone morphogenetic protein (BMP) antagonist vital for tooth regeneration that is expressed in kidney, gingiva, and dental tissues.

We analyzed recent studies focusing on USAG‐1 and its involvement in BMP and Wnt signaling pathways related to dental tissue repair and regeneration. Preclinical models and clinical trial data were examined to evaluate the efficacy of USAG‐1 inhibition as a therapeutic strategy. In addition, publicly available single‐cell RNA sequencing and STRING databases were analyzed to investigate the gene expression of USAG‐1 in human tissues and its protein interactions, respectively.

RNA‐seq analysis confirmed that USAG‐1 is expressed in a subset of secretory cell types in kidney, jaw, and gingiva that are important for cell growth and morphogenesis. Recent studies have also demonstrated that inhibiting USAG‐1 facilitates tooth regeneration by activating BMP‐mediated morphogenesis and improving outcomes in preclinical models. Engineered monoclonal antibodies that target USAG‐1 have shown that blocking the protein product of this gene can promote third dentition and alleviate congenital tooth agenesis. Clinical trials utilizing this antibody are currently underway, with prospects for commercial applications within the next decade. Despite these advancements, challenges related to safety, specificity, and delivery mechanisms remain.

This review underscores the transformative potential of USAG‐1‐based therapies in regenerative dentistry, offering a paradigm shift in dental care by enabling biologically authentic tooth regeneration. However, the realization of these advancements in clinical practice requires overcoming significant barriers, including ensuring safety, optimizing delivery systems, and addressing ethical concerns. Continued interdisciplinary research is essential to fully harness the potential of USAG‐1 in regenerative dentistry.