Anti-USAG-1 therapy for tooth regeneration through enhanced BMP signaling

 

Anti-USAG-1 therapy for tooth regeneration through enhanced BMP signaling

A Murashima-Suginami 1, H Kiso 1, Y Tokita 2, E Mihara 3, Y Nambu 4, R Uozumi 5, Y Tabata 6, K Bessho 1, J Takagi 3, M Sugai 7 8, K Takahashi 9
Affiliations 

Abstract

Uterine sensitization-associated gene-1 (USAG-1) deficiency leads to enhanced bone morphogenetic protein (BMP) signaling, leading to supernumerary teeth formation. Furthermore, antibodies interfering with binding of USAG-1 to BMP, but not lipoprotein receptor-related protein 5/6 (LRP5/6), accelerate tooth development. Since USAG-1 inhibits Wnt and BMP signals, the essential factors for tooth development, via direct binding to BMP and Wnt coreceptor LRP5/6, we hypothesized that USAG-1 plays key regulatory roles in suppressing tooth development. However, the involvement of USAG-1 in various types of congenital tooth agenesis remains unknown. Here, we show that blocking USAG-1 function through USAG-1 knockout or anti-USAG-1 antibody administration relieves congenital tooth agenesis caused by various genetic abnormalities in mice. Our results demonstrate that USAG-1 controls the number of teeth by inhibiting development of potential tooth germs in wild-type or mutant mice missing teeth. Anti-USAG-1 antibody administration is, therefore, a promising approach for tooth regeneration therapy.

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