While most people have 32 teeth, around 1% of the population has more or fewer due to congenital reasons. Now, researchers from Kyoto University and the University of Fukui in Japan have found that an antibody for a certain gene can stimulate teeth to grow in mice with tooth agenesis, a condition in which teeth are missing.
Teeth are formed from interactions between several molecules including bone morphogenetic protein (BMP) and wingless/integrated (Wnt) signaling pathways that regulate cell growth, motility, and differentiation during embryonic development. Beyond tooth development, both are also involved in the growth of multiple organs and tissues. Due to this, drugs that affect their activity are usually avoided due to their potential side effects.
To avoid negative side effects from tampering directly with BMP and Wnt signaling, the researchers sought to target factors that antagonize them during tooth development. Following this, they targeted a gene known as uterine sensitization associated gene-1 (USAG-1). While they knew that suppressing the gene was beneficial for tooth growth, they did not know exactly what effect it would have on tooth agenesis.
During experiments with mice, they tried several monoclonal antibodies for USAG-1. While many of these antibodies led to poor birth and survival rates among mice, one managed to disrupt the interaction of USAG-1 with BMP alone. Experimenting with this antibody demonstrated that BMP signaling is crucial for determining the number of teeth mice have, and that a single dose is sufficient to generate an entire tooth.
To see whether their findings extended across species, the scientists also tested the antibody on ferrets, as they have similar dental patterns to humans. These experiments were once again successful. As such, the researchers now plan to test the antibodies on other animals such as pigs and dogs.
"Conventional tissue engineering is not suitable for tooth regeneration. Our study shows that cell-free molecular therapy is effective for a wide range of congenital tooth agenesis," says Manabu Sugai, one of the study’s authors.