It may be possible to regenerate missing teeth using monoclonal antibodies, according to a new study by scientists at Kyoto University and the University of Fukui.
The team reported that an antibody for one gene—uterine sensitisation associated gene-1 or USAG-1—can stimulate tooth growth in mice suffering from tooth agenesis, a congenital condition. The paper was published in Science Advances. Monoclonal antibodies are often used to treat cancers, arthritis, and vaccine development.
Although the normal adult mouth has 32 teeth, about 1% of the population has more or fewer due to congenital conditions; adults with too many teeth are of interest because they could hold genetic clues to tooth regeneration.
Katsu Takahashi, one of the lead authors of the study and a senior lecturer at the Kyoto University Graduate School of Medicine, said that the fundamental molecules responsible for tooth development have already been identified.
“The morphogenesis of individual teeth depends on the interactions of several molecules including BMP, or bone morphogenetic protein, and Wnt signaling,” said Takahashi.
BMP and Wnt are also involved in the development of organs when humans are mere embryos. This means that drugs directly affecting their activity are usually avoided, as side effects could impact the entire body. The team considered the gene USAG-1, as they guessed that it could be safer to target the factors that antagonise BMP and Wnt specifically in tooth development .
“We knew that suppressing USAG-1 benefits tooth growth. What we did not know was whether it would be enough,” added Takahashi.
The scientists therefore investigated the effects of several monoclonal antibodies for USAG-1. Since USAG-1 interacts with both BMP and Wnt, many of the antibodies resulted in poor birth and survival rates of mice, showing that BMP and Wnt are important for whole body growth. However one antibody managed to disrupt the interaction of USAG-1 with BMP only.
Experimentation showed that BMP signalling is necessary for the number of teeth in mice, and a single administration was enough to generate an entire tooth. The same effects were seen 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,” explains Takahashi.
This is the first study to show the benefits of monoclonal antibodies on tooth regeneration, and offers new alternatives to implants.
“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,” concluded Manabu Sugai of the University of Fukui, another author of the study.
Source: Medical Xpress
Journal information: A. Murashima-Suginami et al, Anti–USAG-1 therapy for tooth regeneration through enhanced BMP signaling, Science Advances (2021). DOI: 10.1126/sciadv.abf1798
