Suppressing a gene known as USAG-1 by using its antibody may efficiently lead to tooth growth, according to researchers at Kyoto University and the University of Fukui.
Specifically, the antibody for uterine sensitization associated gene-1 (USAG-1) can stimulate tooth growth in mice suffering from tooth agenesis, a congenital condition.
Although normal adults have 32 teeth, about 1% of the population has more or fewer teeth due to congenital conditions. Scientists have explored the genetic causes for cases having too many teeth as clues for regenerating teeth in adults. In fact, the fundamental molecules responsible for tooth development already have been identified.
“The morphogenesis of individual teeth depends on the interactions of several molecules including BMP, or bone morphogenetic protein, and Wnt signaling,” said lead author Katsu Takahashi, a senior lecturer at the Kyoto University Graduate School of Medicine.
BMP and Wnt are involved in much more than tooth development, the researchers said. They also modulate the growth of multiple organs and tissues well before the human body is even the size of a raisin.
Consequently, the researchers said, drugs that directly affect their activity are commonly avoided, since side effects could affect the entire body.
Guessing that targeting the factors that antagonize BMP and Wnt specifically in tooth development could be safer, the researchers considered USAG-1.
“We know that suppressing USAG-1 benefits tooth growth. What we did not know was whether it would be enough,” said Takahashi.
The researchers then investigated the effects of several monoclonal antibodies for USAG-1. Monoclonal antibodies are commonly used to treat cancers, arthritis, and vaccine development.
USAG-1 interacts with both BMP and Wnt. As a result, several of the antibodies led to poor birth and survival rates of the mice, affirming the importance of both BMP and Wnt on whole body growth. One promising antibody, however, disrupted the interaction of USAG-1 with BMP only.
Experiments with this antibody revealed that BMP signaling is essential for determining the number of teeth in mice. Moreover, a single administration was enough to generate a whole tooth. Subsequent experiments showed the same benefits in ferrets.
“Ferrets are diphyodont animals with similar dental patterns to humans. Our next plan is to test the antibodies on other animals such as pigs and dogs,” said Takahashi.
The study is the first to show the benefits of monoclonal antibodies on tooth regeneration and provides a new therapeutic framework for a clinical problem that can currently only be resolved with implants and other artificial measures, the researchers said.
“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,” said author Manabu Sugai of the University of Fukui.
The study, “Anti-USAG-1 Therapy for Tooth Regeneration Through Enhanced BMP Signaling,” was published by Science Advances.
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