International Journal of Scientific Research and Engineering Development

Background:
Tooth agenesis is a common developmental anomaly that affects mastication, esthetics, and psychosocial wellbeing. Conventional treatments such as dentures, bridges, and implants can restore function but cannot regenerate living dental tissues. USAG-1, a dual antagonist of BMP and Wnt pathways, has emerged as a keyinhibitory regulator of tooth number, making it a promising molecular target for activating dormant thirddentition potential. This review aims to summarize current experimental evidence on USAG-1 inhibition as a biological approach to tooth regeneration.
Methods:
A systematic search of PubMed, ScienceDirect, and Google Scholar (2019–2025) identified in vitro, in vivo,and preclinical studies evaluating USAG-1 modulation through gene knockout, siRNA delivery, ormonoclonal antibodies. Studies lacking primary data or unrelated to odontogenesis were excluded.
Results:
Across major investigations, USAG-1 inhibition consistently restored tooth development in congenitalagenesis models. Gene knockout animals produced supernumerary teeth due to enhanced odontogenic signaling. Local delivery of USAG-1 siRNA reactivated arrested tooth germs, demonstrating effective sitespecific regeneration. Neutralizing antibodies further induced new teeth and rescued agenesis in multiple mammalian models, producing enamel–dentin structures similar to natural dentition. Genetic evidence supports USAG-1 as a central molecular switch coordinating key odontogenic pathways.
Conclusion:
Current findings establish USAG-1 inhibition as a promising strategy for activating third-dentition tooth formation. The development of humanized anti-USAG-1 antibodies represents a significant translational step toward future clinical applications in regenerative dentistry.

Rafael Gerrard, Evelyn Nathania Prasetyo, Rhemadhyaksa Tegar Arrondiwa, Rachffa Ramadhan Putra Prakoso, Bryan Moslem Saifullah, Tasya Nuura Pradipta, Andrey, Valerian Rayhan Wijaya, "USAG-1 as a Regenerative Switch: Current Evidence and Future Directions for Third-Dentition-Based Tooth Renewal" International Journal of Scientific Research and Engineering Development, V8(6): Page(2834-2841) Nov-Dec 2025. ISSN: 2581-7175. www.ijsred.com. Published by Scientific and Academic Research Publishing.