A team has reported that an antibody for a single gene stimulates tooth growth and regenerates lost teeth in mice suffering from tooth agenesis.
Teeth are ectodermal organs. Their development is regulated by a signal transduction network involving interactions between the epithelium and mesenchyme. While the number is strictly controlled in individual species, in about 1% of individuals it can increase or decrease. Conditions that increase or decrease the usual number of teeth are known as supernumerary teeth and tooth agenesis, respectively. Research in mouse models has enabled us to delve into the genetic, molecular and also pathological mechanisms underlying these conditions.
Researchers have previously reported that USAG-1 deficient mice experience enhanced bone morphogenetic protein (BMP) signalling, which leads to supernumerary teeth formation. In addition, it has been shown that interfering with binding of USAG-1 to BMP, accelerates tooth development. USAG-1 inhibits Wnt and BMP signals, which are essential in tooth development. This suggests that USAG-1 plays a key regulatory role in suppressing tooth development. However, its role in various types of congenital tooth agenesis remains unknown.
Antibody regenerates lost teeth
In this study, published in Science Advances, researchers aimed to generate and use a monoclonal anti-USAG-1 antibody to locally arrest and recover tooth development.
They showed that blocking USAG-1 function through USAG-1 knockout or anti-USAG-1 antibody administration relieved congenital tooth agenesis caused by various genetic abnormalities in mice. As BMP and Wnt are important for whole body growth, several antibodies led to poor birth and survival rates. However, one promising antibody, disrupted the interaction of USAG-1 with BMP only. The experiments with this antibody revealed that BMP signalling is essential for determining the number of teeth in mice. In addition, a single administration of this antibody was sufficient to generate a whole tooth.
As conventional tissue engineering is not suitable for tooth regenetation, this study demonstrates anti-USAG-1 as a promising approach for tooth regeneration therapy in a wide range of congenital tooth agenesis.
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