A tooth for a mouse

Monoclonal antibodies helped to grow missing teeth in mice

Sergey Vasiliev, Naked Science

Japanese researchers have discovered a gene that regulates the formation of teeth, and have grown new ones in laboratory animals that lacked them. Perhaps in the future this technology will become a therapy and will allow doctors to replace severely damaged teeth in patients with completely healthy new ones. They write about this in an article published in the journal Science Advances (Murashima-Suginami et al., Anti–USAG-1 therapy for tooth regeneration through enhanced BMP signaling).

Katsu Takahashi and his colleagues from the Medical School of Kyoto University worked with mice suffering from a congenital lack or excess of teeth due to genetic disorders. They noticed that animals with the knocked-out USAG-1 gene have more teeth than the normal number (mice should have 32).

The protein encoded by this gene suppresses the work of the BMP and Wnt signaling pathways – complex cascades of protein molecules that regulate the growth and development of many tissues and organs, including teeth. That is why doctors avoid drugs that interfere with their work: the impact will not be spot-on, but will cover almost the entire body, and its "side effects" can far outweigh all the benefits.

However, scientists have suggested that if the "disabled" USAG-1 gene leads to the growth of excess teeth, then its action does not always affect signaling pathways in other tissues. They received and tested various monoclonal antibodies that block the work of USAG-1. Most of them led to dangerous disorders in the body, however, one type of antibody that disrupted the interaction of USAG-1 and the BMP pathway, but did not affect the Wnt pathway, turned out to be more selective. In one case, a single injection of antibodies was enough for the mouse to fully form a whole missing tooth.

Photo: Kyoto University/Katsu Takahashi

Similar results with antibodies to USAG-1 were obtained on ferrets – like humans, these animals are difiodont and change two generations of teeth in a lifetime. Now Japanese scientists plan to continue testing a promising new approach and test it on animals even closer to us, such as dogs and pigs. Earlier, Chinese scientists demonstrated the possibility of growing tooth enamel – for those future patients who do not need to replace a whole tooth.

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