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

• Murashima-Suginami, A.

• Kiso, H.

• Tokita, Y.

• Mihara, E.

• Nambu, Y.

• Uozumi, R.

• Tabata, Y.

• Bessho, K.

• Takagi, J.

• Sugai, M.

• Takahashi, K.

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.

先天性無歯症に対する分子標的薬の開発 --USAG-1を標的分子とした歯再生治療--. 京都大学プレスリリース. 2021-02-15.

Journal

• Science Advances

  Science Advances 7 (7), 7-, 2021-02-10

  American Association for the Advancement of Science (AAAS)

Keywords

• Multidisciplinary

Details

• CRID: 1050005667203086336
• NII Article ID: 120006958083
• ISSN: 23752548
• DOI: 10.1126/sciadv.abf1798
• HANDLE: 2433/261703
• Web Site: https://www.science.org/doi/pdf/10.1126/sciadv.abf1798
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN