Artificial Teeth and Biological Tooth Regeneration Through USAG-1 Suppression: A Narrative Review

Abstract

Tooth loss remains one of the most common oral health problems worldwide and continues to impose a substantial burden on aesthetics, nutrition, and quality of life. Conventional prosthetic rehabilitation with artificial teeth and dental implants restores function predictably, but it cannot fully reproduce the biology of a natural tooth. Recent work has highlighted the significance of suppressing Uterine Sensitization-Associated Gene-1 (USAG-1, also known as SOSTDC1) as a means of achieving biological tooth regeneration. This narrative review summarizes the published evidence on established modalities of artificial tooth replacement and on the emerging regenerative approach based on USAG-1 inhibition. The literature was searched in PubMed, Scopus, Embase, and Google Scholar for the period January 2015 to March 2026. USAG-1 is a secreted antagonist of the Bone Morphogenetic Protein (BMP) and Wnt pathways, both of which are essential to odontogenesis. Its suppression in animal models — by gene knockout, small interfering RNA, or neutralizing monoclonal antibodies — enhances BMP signalling and induces supernumerary tooth formation and the rescue of congenital tooth agenesis, with effects demonstrated in mice and subsequently in a non-rodent (ferret) model. A humanized anti-USAG-1 antibody has since completed non-clinical safety testing and entered first-in-human evaluation, marking the transition of this approach from preclinical proof of concept toward clinical translation. Artificial teeth remain the standard of care, but biological tooth regeneration represents a promising future alternative. Long-term clinical data on safety, efficacy, control of tooth morphology and eruption, and cost-effectiveness are still required before routine application can be considered.