USAG-1/SOSTDC1 as a Candidate Target for Periodontal Regeneration: Biological Rationale, Knowledge Gaps, and Future Directions

Background

Uterine Sensitization-Associated Gene-1 (USAG-1), also known as SOSTDC1, is a bifunctional antagonist of bone morphogenetic protein (BMP) and Wnt signalling—two pathways that are central not only to tooth development but to the entire repertoire of periodontal tissue biology. Current periodontal regenerative therapy relies on exogenous BMP delivery and barrier membranes, approaches with significant limitations in predictability and tissue specificity. The recent entry of anti-USAG-1 antibody therapy into early-phase human clinical trials, with congenital tooth agenesis as the lead indication, raises the question of whether targeted USAG-1 inhibition could be repurposed for periodontal regeneration.