False teeth could one day be a thing of the past, thanks to the discovery of an antibody that sparks the regeneration of lost teeth. By inhibiting the action of a gene called USAG-1, the antibody increases the availability of certain growth factors, and could eventually be used to help people grow a new set of pearly whites. Publishing their work in the journal Science Advances, a team of researchers describes how they genetically modified mice to suffer from tooth agenesis, where some teeth fail to develop. Injecting pregnant mice from this line with the USAG-1 antibody, however, resulted in normal tooth development among their offspring. Moreover, a single administration of the antibody caused the growth of a whole new tooth in regular mice. The researchers decided to target the USAG-1 gene because it is known to inhibit two signaling molecules known as BMP and Wnt, both of which are involved in tooth development. However, because these compounds also control the growth of a wide range of other organs, interfering with them can produce an array of serious side-effects. During their experiments, the team tested a number of different monoclonal antibodies that alter the ability of USAG-1 to interact with both BMP and Wnt, although several of these produced serious birth defects. Eventually, though, they hit upon a particular antibody that prevented the gene from binding with BMP, but had no impact on Wnt. In doing so, they were able to stimulate tooth growth without producing any other unwanted effects. Based on this finding, the authors conclude that USAG-1 prevents the growth of teeth by binding to BMP, thereby reducing its activity. In a statement, study author Katsu Takahashi explained that "we knew that suppressing USAG-1 benefits tooth growth. What we did not know was whether it would be enough." Yet the team’s results indicate that inhibiting the gene’s activity allows for a sufficient increase in BMP for the growth of new teeth. While this technique is nowhere near ready to be trialed on humans, the researchers did test the antibody on ferrets. These animals have similar dental patterns to humans, and, like us, are diphyodont, meaning they have a set of milk teeth that are later replaced by adult teeth. Results indicated that the treatment is just as effective for ferrets, with a single dose of the antibody sparking the generation of a whole tooth. This suggests that the technique may work for humans, too, although a number of safety concerns will need to be overcome before this can be tested. For now, the researchers say they are planning to repeat the experiment on other mammals such as pigs and dogs. Source
