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Updated: Jul 4, 2025

Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein
Published on: June 16, 2023
EBAG9-deficient mice display decreased bone mineral density with suppressed autophagy
Kotaro Azuma1,2, Kazuhiro Ikeda3, Sachiko Shiba3
1Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
Abstract:
Estrogen receptor-binding fragment associated antigen 9 (EBAG9) exerts tumor-promoting effects by inducing immune escape. We focused on the physiological functions of EBAG9 by investigating the bone phenotypes of Ebag9-knockout mice. Female Ebag9-knockout mice have fragile bones with lower bone mineral density (BMD) compared with wild-type mice. Histomorphometric analyses demonstrated that lower BMD was mainly caused by decreased bone formation. Serum bone turnover markers showed that enhanced bone resorption also contributed to this phenotype. We revealed that EBAG9 promoted autophagy in both osteoblastic and osteoclastic lineages. In addition, the knockdown of Tm9sf1, a gene encoding a protein that functionally interacts with EBAG9, suppressed autophagy and osteoblastic differentiation of the murine preosteoblastic cell line MC3T3-E1. Finally, overexpression of TM9SF1 rescued the suppression of autophagy caused by the silencing of Ebag9. These results suggest that EBAG9 plays a physiological role in bone maintenance by promoting autophagy together with its interactor TM9SF1.
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